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.14815G>A (p.Asp4939Asn)

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA024262

201153 (ClinVar)

Gene: RYR1

Condition: RYR1-related myopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 3e422971-0629-471d-9f42-3bbcf18ccf74

Approved on: 2024-08-27

Published on: 2025-01-03

HGVS expressions

NM_000540.3:c.14815G>A

NM_000540.3(RYR1):c.14815G>A (p.Asp4939Asn)

NC_000019.10:g.38585949G>A

CM000681.2:g.38585949G>A

NC_000019.9:g.39076589G>A

CM000681.1:g.39076589G>A

NC_000019.8:g.43768429G>A

NG_008866.1:g.157250G>A

ENST00000593677.2:c.1751G>A

ENST00000688602.1:c.3148G>A

ENST00000689936.1:c.3120G>A

ENST00000692547.1:n.208G>A

ENST00000359596.8:c.14815G>A

ENST00000355481.8:c.14800G>A

ENST00000359596.7:c.14815G>A

ENST00000360985.7:c.14797G>A

NM_000540.2:c.14815G>A

NM_001042723.1:c.14800G>A

NM_001042723.2:c.14800G>A

Uncertain Significance

PP3 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.14815G>A in RYR1 is a missense variant predicted to cause substitution of aspartic acid by asparagine at amino acid 4939 (p.Asp4939Asn). The highest population minor allele frequency in gnomAD v4.1 is 0.00001562 (1/64012 alleles) for the European) non-Finnish population, meeting PM2_Supporting. The REVEL computational prediction analysis tool produced a score of 0.811, which is above the threshold necessary to apply PP3. Since this variant has not been noted in any probands, the mode of inheritance is unknown. 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: PP3, PM2_Supporting. (Congenital Myopathies VCEP specifications version 2; 8/27/2024).

PP3

The REVEL computational prediction analysis tool produced a score of 0.811, which is above the threshold necessary to apply PP3.

PM2_Supporting

The highest population minor allele frequency in gnomAD v4.1 is 0.00001562 (1/64012 alleles) for the European) non-Finnish population, meeting PM2_Supporting.

Curation History

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