owencqueen/cgbench_data huggingface dataset:
Gene: RYR1 (HGNC:10483)
Evidence Code: PS1 — Moderate
Modification Type: Strength
Same amino acid change as a previously established likely pathogenic variant regardless of nucleotide change.




Previously established likely pathogenic variant must reach a classification of likely pathogenic without PS1.
Gene: RYR1 (HGNC:10483)
Evidence Code: PS4 — Strong
Modification Type: Strength,Disease-specific
The prevalence of the variant in affected individuals significantly increased compared with the prevalence in controls.




≥7 MH case points. Probands with a personal or family history of an MH event are awarded 0.5 points, probands with a personal or family history of a positive (MHS) IVCT/CHCT are awarded an additional 0.5 points. Probands with multiple variants in RYR1 classified as VUS, likely pathogenic or pathogenic are not considered. Popmax in gnomAD ≤0.00006.


For variants with popmax MAF gnomAD >0.00006, an odds ratio of ≥18.7 when comparing MH case points to allele count in gnomAD can qualify. Popmax in gnomAD must be <0.0038.
Gene: RYR1 (HGNC:10483)
Evidence Code: PS4 — Moderate
Modification Type: Strength,Disease-specific
The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls.




2-6 MH case points. Probands with a personal or family history of an MH event are awarded 0.5 points, probands with a personal or family history of a positive (MHS) IVCT/CHCT are awarded an additional 0.5 points. Probands with multiple variants in RYR1 classified as VUS, likely pathogenic or pathogenic are not considered. Popmax in gnomAD ≤0.00006.


For variants with popmax MAF in gnomAD >0.00006, an odds ratio of ≥4.33 when comparing MH case points to allele count in gnomAD can qualify. Popmax in gnomAD must be <0.0038.
Gene: RYR1 (HGNC:10483)
Evidence Code: PS4 — Supporting
Modification Type: Strength,Disease-specific
The prevalence of the variant in affected individuals is significantly increased compared withthe prevalence in controls.




1 MH case point. Probands with a personal or family history of an MH event are awarded 0.5 points, probands with a personal or family history of a positive (MHS) IVCT/CHCT are awarded an additional 0.5 points. Probands with multiple variants in RYR1 classified as VUS, likely pathogenic or pathogenic are not considered. Popmax in gnomAD ≤0.00006.
For variants with popmax MAF in gnomAD >0.00006, an odds ratio of ≥2.08 when comparing MH case points to allele count in gnomAD can qualify. Popmax in gnomAD must be <0.0038.
Gene: RYR1 (HGNC:10483)
Evidence Code: PM1 — Moderate
Modification Type: Disease-specific
Located in a mutational hot spot and/or critical and well established functional domain.




Residues 1-552 (N-terminal region) and 2,101-2,458 (central region) 


PM1 should not be applied at a moderate weight with PS1/PM5, see PM1_Supporting.
Gene: RYR1 (HGNC:10483)
Evidence Code: PM1 — Supporting
Modification Type: Strength,Disease-specific
Located in a mutational hot spot and/or critical and well established functional domain.




Residues 1-552 (N-terminal region) and 2,101-2,458 (central region), if PS1/PM5 applicable then PM1 should be used at supporting 


Residues 4,631-4,991 (C-terminal region).
Gene: RYR1 (HGNC:10483)
Evidence Code: PM5 — Supporting
Modification Type: Strength,Disease-specific
Missense change at an amino acid residue where a different missense variant previously determined to be pathogenic.




Previously established likely pathogenic variant can be considered supporting evidence, must reach a classification of likely pathogenic without PM5.


Grantham score for alternate likely pathogenic variant must be less than for variant being assessed.