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NM_001035.3(RYR2):c.527G>A (p.Arg176Gln) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 1, 2019
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:
RCV002345634.9

Allele description [Variation Report for NM_001035.3(RYR2):c.527G>A (p.Arg176Gln)]

NM_001035.3(RYR2):c.527G>A (p.Arg176Gln)

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.527G>A (p.Arg176Gln)
Other names:
p.R176Q:CGA>CAA
HGVS:
  • NC_000001.11:g.237377386G>A
  • NG_008799.3:g.340203G>A
  • NM_001035.3:c.527G>AMANE SELECT
  • NP_001026.2:p.Arg176Gln
  • LRG_402t1:c.527G>A
  • LRG_402:g.340203G>A
  • LRG_402p1:p.Arg176Gln
  • NC_000001.10:g.237540686G>A
  • NG_008799.2:g.339985G>A
  • NM_001035.2:c.527G>A
  • Q92736:p.Arg176Gln
Protein change:
R176Q
Links:
UniProtKB: Q92736#VAR_044087; dbSNP: rs794728708
NCBI 1000 Genomes Browser:
rs794728708
Molecular consequence:
  • NM_001035.3:c.527G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002643007Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Oct 1, 2019) 		germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2).

Tiso N, Stephan DA, Nava A, Bagattin A, Devaney JM, Stanchi F, Larderet G, Brahmbhatt B, Brown K, Bauce B, Muriago M, Basso C, Thiene G, Danieli GA, Rampazzo A.

Hum Mol Genet. 2001 Feb 1;10(3):189-94.

PubMed [citation]
PMID:
11159936

Spectrum and prevalence of cardiac ryanodine receptor (RyR2) mutations in a cohort of unrelated patients referred explicitly for long QT syndrome genetic testing.

Tester DJ, Kopplin LJ, Will ML, Ackerman MJ.

Heart Rhythm. 2005 Oct;2(10):1099-105.

PubMed [citation]
PMID:
16188589
See all PubMed Citations (11)

Details of each submission

From Ambry Genetics, SCV002643007.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

The p.R176Q pathogenic mutation (also known as c.527G>A), located in coding exon 8 of the RYR2 gene, results from a G to A substitution at nucleotide position 527. The arginine at codon 176 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in association with arrhythmia phenotypes, including detection in individuals with syncope with and without reported QTc prolongation, and catecholaminergic polymorphic ventricular tachycardia (CPVT) (Tester DJ et al. Heart Rhythm, 2005 Oct;2:1099-105; Medeiros-Domingo A et al. J. Am. Coll. Cardiol., 2009 Nov;54:2065-74; Berge KE et al. Scand. J. Clin. Lab. Invest., 2008;68:362-8; Haugaa KH et al. Europace, 2010 Mar;12:417-23). This alteration has also been reported to co-occur with a second RYR2 variant in a family with arrhythmogenic right ventricular cardiomyopathy (Tiso N et al. Hum. Mol. Genet., 2001 Feb;10:189-94). In addition, inducible ventricular arrhythmias including bi-directional and polymorphic ventricular tachycardia have been demonstrated in mouse models expressing p.R176Q (Kannankeril PJ et al. Proc. Natl. Acad. Sci. U.S.A., 2006 Aug;103:12179-84; Li N. Int. J. Cardiol. 2017 Jan;227:668-673). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: May 26, 2024