Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000540.3(RYR1):c.10100A>G (p.Lys3367Arg)

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA023815

65956 (ClinVar)

Gene: RYR1

Condition: RYR1-related myopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 3c33e464-bfda-48b5-abfd-628a4461bd5d

Approved on: 2024-11-18

Published on: 2025-04-02

HGVS expressions

NM_000540.3:c.10100A>G

NM_000540.3(RYR1):c.10100A>G (p.Lys3367Arg)

NC_000019.10:g.38519295A>G

CM000681.2:g.38519295A>G

NC_000019.9:g.39009935A>G

CM000681.1:g.39009935A>G

NC_000019.8:g.43701775A>G

NG_008866.1:g.90596A>G

ENST00000599547.6:c.10039A>G

ENST00000359596.8:c.10100A>G

ENST00000355481.8:c.10100A>G

ENST00000359596.7:c.10100A>G

ENST00000360985.7:c.10097A>G

ENST00000594335.5:c.3502A>G

ENST00000599547.5:c.907A>G

NM_000540.2:c.10100A>G

NM_001042723.1:c.10100A>G

NM_001042723.2:c.10100A>G

Uncertain Significance

PS4_Supporting PM2_Supporting

Evidence Links 0

Expert Panel

Congenital Myopathies VCEP

Criteria Specification Information

Criteria Specification: ClinGen Congenital Myopathies Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RYR1 Version 2.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Congenital Myopathies VCEP

The variant NM_000540.3:c.10100A>G in RYR1 is a missense variant predicted to cause substitution of lysine by arginine at amino acid 3367 (p.Lys3367Arg). The variant is absent from gnomAD v4.1.0 (PM2_Supporting). The computational predictor REVEL gives a score of 0.632, which is neither above nor below the thresholds predicting a damaging or benign impact on RYR1 function. This variant has been reported in one proband with central core disease (PS4_Supporting; PMID: 16621918). In summary, this variant meets the criteria to be classified as uncertain significance for AD RYR1-related myopathy. ACMG/AMP criteria met, as specified by the Congenital Myopathies VCEP (Specification Version 1.0.0): PM2_Supporting, PS4_Supporting (ClinGen Congenital Myopathies VCEP specifications version 2.0.0; 11/18/2024).

PS4_Supporting

A proband was reported with one PP4 feature met (central cores present), scoring 0.25 points and meeting PS4_Supporting (PMID: 16621918)

PM2_Supporting

This variant was not present in GnomAD v4.1.0

Curation History

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