Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000540.3(RYR1):c.619C>T (p.Arg207Cys)

CA067890

212104 (ClinVar)

Gene: RYR1
Condition: RYR1-related myopathy
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 6ea47f2e-7ebf-41f1-b31c-4c88863065ef
Approved on: 2024-08-27
Published on: 2025-01-03

HGVS expressions

NM_000540.3:c.619C>T
NM_000540.3(RYR1):c.619C>T (p.Arg207Cys)
NC_000019.10:g.38444665C>T
CM000681.2:g.38444665C>T
NC_000019.9:g.38935305C>T
CM000681.1:g.38935305C>T
NC_000019.8:g.43627145C>T
NG_008866.1:g.15966C>T
ENST00000599547.6:c.619C>T
ENST00000359596.8:c.619C>T
ENST00000355481.8:c.619C>T
ENST00000359596.7:c.619C>T
ENST00000360985.7:c.619C>T
NM_000540.2:c.619C>T
NM_001042723.1:c.619C>T
NM_001042723.2:c.619C>T
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Uncertain Significance

Not Met criteria codes 5
PM2 BS1 BP4 BA1 PP3

Evidence Links 0

Expert Panel

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 c.619C>T variant in RYR1 is a missense variant predicted to cause substitution of arginine by cysteine at amino acid 207 (p.Arg207Cys). The highest population minor allele frequency in gnomAD v4.1 is 0.00001017 (12/1179596 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met). The computational predictor REVEL gives a score of 0.459, which is neither above nor below the thresholds predicting a damaging or benign impact on RYR1 function. In summary, this variant meets the criteria to be classified as uncertain significance for AD/AR RYR1-related myopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen Congenital Myopathies VCEP: None. (ClinGen Congenital Myopathies VCEP specifications version 2; 08/27/2024)
Not Met criteria codes
PM2
The highest population minor allele frequency in gnomAD v4.1 is 0.00001017 (12/1179596 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
BS1
The highest population minor allele frequency in gnomAD v4.1 is 0.00001017 (12/1179596 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
BP4
The computational predictor REVEL gives a score of 0.459, which is neither above nor below the thresholds predicting a damaging or benign impact on RYR1 function.
BA1
The highest population minor allele frequency in gnomAD v4.1 is 0.00001017 (12/1179596 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
PP3
The computational predictor REVEL gives a score of 0.459, which is neither above nor below the thresholds predicting a damaging or benign impact on RYR1 function.
Curation History
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