AVCG pathogenicity classifications

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BS1 Doesn't track with the disease. It fails to co-occur with the disease in affected members of a family.
• BP5 Case had another cause. It was found in a case that already has a different molecular cause for the disease.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BP5 Case had another cause. It was found in a case that already has a different molecular cause for the disease.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS1 Same change as a known cause. It makes the exact same protein change as a variant already proven to cause disease (even if the DNA spelling differs).
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BS1 Doesn't track with the disease. It fails to co-occur with the disease in affected members of a family.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM2 A new change at a known-critical spot. It changes a protein building block at a position where a different change has already been shown to cause disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS1 Same change as a known cause. It makes the exact same protein change as a variant already proven to cause disease (even if the DNA spelling differs).
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM2 A new change at a known-critical spot. It changes a protein building block at a position where a different change has already been shown to cause disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BP1 Not conserved + clear elsewhere. The position is not conserved across species, and other species' data point to it being harmless.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS1 Same change as a known cause. It makes the exact same protein change as a variant already proven to cause disease (even if the DNA spelling differs).
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM2 A new change at a known-critical spot. It changes a protein building block at a position where a different change has already been shown to cause disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BS1 Doesn't track with the disease. It fails to co-occur with the disease in affected members of a family.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS1 Same change as a known cause. It makes the exact same protein change as a variant already proven to cause disease (even if the DNA spelling differs).
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BS1 Doesn't track with the disease. It fails to co-occur with the disease in affected members of a family.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS2 Arose new in an affected animal. It appeared new in an affected animal whose parents were tested and do not carry it.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS1 Same change as a known cause. It makes the exact same protein change as a variant already proven to cause disease (even if the DNA spelling differs).
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM2 A new change at a known-critical spot. It changes a protein building block at a position where a different change has already been shown to cause disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BS1 Doesn't track with the disease. It fails to co-occur with the disease in affected members of a family.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BS1 Doesn't track with the disease. It fails to co-occur with the disease in affected members of a family.
• BP5 Case had another cause. It was found in a case that already has a different molecular cause for the disease.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BS1 Doesn't track with the disease. It fails to co-occur with the disease in affected members of a family.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS2 Arose new in an affected animal. It appeared new in an affected animal whose parents were tested and do not carry it.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM2 A new change at a known-critical spot. It changes a protein building block at a position where a different change has already been shown to cause disease.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM2 A new change at a known-critical spot. It changes a protein building block at a position where a different change has already been shown to cause disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS1 Same change as a known cause. It makes the exact same protein change as a variant already proven to cause disease (even if the DNA spelling differs).
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BS2 Seen in healthy adults. It's found in healthy adults in a form (homozygous, heterozygous, or hemizygous) that should already have caused disease if it were harmful.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS2 Arose new in an affected animal. It appeared new in an affected animal whose parents were tested and do not carry it.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS2 Arose new in an affected animal. It appeared new in an affected animal whose parents were tested and do not carry it.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BP4 Computers agree it's harmless. Every computational predictor agrees the variant is likely harmless.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS2 Arose new in an affected animal. It appeared new in an affected animal whose parents were tested and do not carry it.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS2 Arose new in an affected animal. It appeared new in an affected animal whose parents were tested and do not carry it.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS2 Arose new in an affected animal. It appeared new in an affected animal whose parents were tested and do not carry it.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS2 Arose new in an affected animal. It appeared new in an affected animal whose parents were tested and do not carry it.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM2 A new change at a known-critical spot. It changes a protein building block at a position where a different change has already been shown to cause disease.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM3 Paired with a known cause (recessive). For a recessive disease, it was found on the opposite gene copy from a known pathogenic variant.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM2 A new change at a known-critical spot. It changes a protein building block at a position where a different change has already been shown to cause disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM2 A new change at a known-critical spot. It changes a protein building block at a position where a different change has already been shown to cause disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PM3 Paired with a known cause (recessive). For a recessive disease, it was found on the opposite gene copy from a known pathogenic variant.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BS1 Doesn't track with the disease. It fails to co-occur with the disease in affected members of a family.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM2 A new change at a known-critical spot. It changes a protein building block at a position where a different change has already been shown to cause disease.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BS1 Doesn't track with the disease. It fails to co-occur with the disease in affected members of a family.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS2 Arose new in an affected animal. It appeared new in an affected animal whose parents were tested and do not carry it.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BP4 Computers agree it's harmless. Every computational predictor agrees the variant is likely harmless.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM2 A new change at a known-critical spot. It changes a protein building block at a position where a different change has already been shown to cause disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BS2 Seen in healthy adults. It's found in healthy adults in a form (homozygous, heterozygous, or hemizygous) that should already have caused disease if it were harmful.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS2 Arose new in an affected animal. It appeared new in an affected animal whose parents were tested and do not carry it.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS2 Arose new in an affected animal. It appeared new in an affected animal whose parents were tested and do not carry it.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BP4 Computers agree it's harmless. Every computational predictor agrees the variant is likely harmless.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM2 A new change at a known-critical spot. It changes a protein building block at a position where a different change has already been shown to cause disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM3 Paired with a known cause (recessive). For a recessive disease, it was found on the opposite gene copy from a known pathogenic variant.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BS1 Doesn't track with the disease. It fails to co-occur with the disease in affected members of a family.
• BP1 Not conserved + clear elsewhere. The position is not conserved across species, and other species' data point to it being harmless.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM2 A new change at a known-critical spot. It changes a protein building block at a position where a different change has already been shown to cause disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS2 Arose new in an affected animal. It appeared new in an affected animal whose parents were tested and do not carry it.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM3 Paired with a known cause (recessive). For a recessive disease, it was found on the opposite gene copy from a known pathogenic variant.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BP4 Computers agree it's harmless. Every computational predictor agrees the variant is likely harmless.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS3 Lab studies show harm. Well-run laboratory studies (in cells or animals) show the variant damages the gene or its protein.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BP2 Pattern argues against cause. It's found alongside a known pathogenic variant in a pattern that argues against this one being the cause.
• BP5 Case had another cause. It was found in a case that already has a different molecular cause for the disease.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.
• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM4 Changes the protein's length. It changes the protein's length (an in-frame insertion or deletion, or a lost stop), outside a repetitive region.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS5 Tracks with the disease in families. It co-occurs with the disease across multiple affected family members, in a gene firmly tied to the disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.
• BP5 Case had another cause. It was found in a case that already has a different molecular cause for the disease.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PVS1 Switches the gene off. The variant shuts the gene down entirely (a premature stop, a frameshift, a core splice-site change, a lost start, or a deleted exon), in a gene where losing function is a known cause of this disease.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.

• PS4 Far more common in affected. The variant is significantly more common in affected animals than in healthy ones.
• PM1 In a critical part of the protein. It sits in a critical, well-mapped region of the protein (like an enzyme's active site) where harmless variation isn't seen across breeds or species.
• PM2 A new change at a known-critical spot. It changes a protein building block at a position where a different change has already been shown to cause disease.
• PP1 Conserved + flagged elsewhere. The position is conserved across species, and data from other species point to it being harmful.
• PP2 Missense in a sensitive gene. It's a missense change in a gene where harmless missense changes are rare and missense changes are a common way disease arises.
• PP3 Computers agree it's damaging. Every computational predictor (conservation, evolution, splicing) agrees the variant is likely damaging.
• PP4 Signs fit the disease precisely. The animal's signs or family history are highly specific to this disease, which has a single genetic cause.

Criteria at least one of the three or more reviewers considered fulfilled, not a per-criterion consensus. The reviewers agreed on the grade, not necessarily on every criterion behind it.