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NM_001035.3(RYR2):c.7570G>A (p.Val2524Ile) AND Cardiomyopathy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 28, 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:
RCV001180243.12

Allele description [Variation Report for NM_001035.3(RYR2):c.7570G>A (p.Val2524Ile)]

NM_001035.3(RYR2):c.7570G>A (p.Val2524Ile)

Gene:
RYR2:ryanodine receptor 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q43
Genomic location:
Preferred name:
NM_001035.3(RYR2):c.7570G>A (p.Val2524Ile)
HGVS:
  • NC_000001.11:g.237649934G>A
  • NG_008799.3:g.612751G>A
  • NM_001035.3:c.7570G>AMANE SELECT
  • NP_001026.2:p.Val2524Ile
  • LRG_402t1:c.7570G>A
  • LRG_402:g.612751G>A
  • LRG_402p1:p.Val2524Ile
  • NC_000001.10:g.237813234G>A
  • NC_000001.10:g.237813234G>A
  • NG_008799.2:g.612533G>A
  • NM_001035.2:c.7570G>A
Protein change:
V2524I
Links:
dbSNP: rs934248102
NCBI 1000 Genomes Browser:
rs934248102
Molecular consequence:
  • NM_001035.3:c.7570G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiomyopathy (CMYO)
Synonyms:
Cardiomyopathies
Identifiers:
MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001345122Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jun 28, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Usefulness of Genetic Testing in Sudden Cardiac Arrest Survivors With or Without Previous Clinical Evidence of Heart Disease.

Asatryan B, Schaller A, Seiler J, Servatius H, Noti F, Baldinger SH, Tanner H, Roten L, Dillier R, Lam A, Haeberlin A, Conte G, Saguner AM, Müller SA, Duru F, Auricchio A, Ammann P, Sticherling C, Burri H, Reichlin T, Wilhelm M, Medeiros-Domingo A.

Am J Cardiol. 2019 Jun 15;123(12):2031-2038. doi: 10.1016/j.amjcard.2019.02.061. Epub 2019 Mar 18.

PubMed [citation]
PMID:
30975432

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 Color Diagnostics, LLC DBA Color Health, SCV001345122.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This missense variant replaces valine with isoleucine at codon 2524 of the RYR2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in a sudden cardiac arrest survivor who did not have previous clinical evidence of heart disease (PMID: 30975432). This individual also carried a truncation variant in the TTN gene. This variant has been identified in 8/280668 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: May 1, 2024