NM_000540.3(RYR1):c.6650G>A (p.Gly2217Asp) AND RYR1-related myopathy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 30, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003994727.1

Allele description [Variation Report for NM_000540.3(RYR1):c.6650G>A (p.Gly2217Asp)]

NM_000540.3(RYR1):c.6650G>A (p.Gly2217Asp)

Gene:
RYR1:ryanodine receptor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.2
Genomic location:
Preferred name:
NM_000540.3(RYR1):c.6650G>A (p.Gly2217Asp)
HGVS:
  • NC_000019.10:g.38496316G>A
  • NG_008866.1:g.67617G>A
  • NG_141317.1:g.582G>A
  • NM_000540.3:c.6650G>AMANE SELECT
  • NM_001042723.2:c.6650G>A
  • NP_000531.2:p.Gly2217Asp
  • NP_000531.2:p.Gly2217Asp
  • NP_001036188.1:p.Gly2217Asp
  • LRG_766t1:c.6650G>A
  • LRG_766:g.67617G>A
  • LRG_766p1:p.Gly2217Asp
  • NC_000019.9:g.38986956G>A
  • NM_000540.2:c.6650G>A
Protein change:
G2217D
Molecular consequence:
  • NM_000540.3:c.6650G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042723.2:c.6650G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
RYR1-related myopathy
Identifiers:
MONDO: MONDO:0100150; MedGen: CN305348

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004812761Molecular Genetics, Royal Melbourne Hospital

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Mar 30, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Molecular Genetics, Royal Melbourne Hospital, SCV004812761.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change in RYR1 is predicted to replace glycine with aspartic acid at codon 2217, p.(Gly2217Asp). The glycine residue is highly conserved (100 vertebrates, UCSC), and is located in exon 40 in the central region, amino acids 2,101-2,458, which is defined as a mutational hotspot. There is a moderate physicochemical difference between glycine and aspartic acid. This variant is absent from the population database gnomAD v2.1 and v3.1. To our knowledge, this variant has not been reported in the literature in any individuals. Multiple lines of computational evidence predict a deleterious effect for the missense substitution (4/5 algorithms). Based on the classification scheme RMH Modified ACMG Guidelines v1.5.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM1, PP3.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 20, 2024