ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.3251G>A (p.Arg1084Lys) (rs193922624)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171675 SCV000055282 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000036727 SCV000060382 likely benign not specified 2014-01-21 criteria provided, single submitter clinical testing Arg1084Lys in exon 28 of RYR2: This variant is not expected to have clinical sig nificance due to a lack of conservation across species, including mammals. Of no te, opossum, tasmanian devil, and wallaby have a lysine (Lys) at this position a s well as several birds and reptiles despite high nearby amino acid conservation . In addition, computational analyses (AlignGVGD, PolyPhen2, SIFT) do not sugges t a high likelihood of impact to the protein. Arg1084Lys in exon 28 of RYR2 (rs 193922624; allele frequency = n/a)
GeneDx RCV000036727 SCV000234991 likely benign not specified 2017-12-01 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000621688 SCV000737629 likely benign Cardiovascular phenotype 2016-07-13 criteria provided, single submitter clinical testing Subpopulation frequency in support of benign classification;In silico models in agreement (benign)
Invitae RCV000694418 SCV000822863 likely benign Catecholaminergic polymorphic ventricular tachycardia 2019-12-15 criteria provided, single submitter clinical testing
Color RCV001190169 SCV001357595 likely benign Cardiomyopathy 2019-11-18 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000030419 SCV000053088 likely benign Cardiac arrhythmia 2015-10-02 no assertion criteria provided clinical testing
Blueprint Genetics RCV000157452 SCV000207196 uncertain significance Primary dilated cardiomyopathy 2014-07-16 no assertion criteria provided clinical testing
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000036727 SCV000280449 uncertain significance not specified 2011-04-14 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p. Arg1084Lys (c.3251G>A) in the RYR2 gene. This variant is novel. It has not been reported in association with disease or as a benign polymorphism. In silico analysis with PolyPhen-2 predicts the variant to be benign. This is a chemically conservative change with a polar positive amino acid replacing another polar positive amino acid. The variant is not conserved across evolution and is in fact a lysine in zebra finch and green puffer. The variant is not listed in dbSNP or 1000 genomes (as of August 2011). Medeiros-Domingo et al (2009) reported that 3% of individuals from the general population carry a rare or novel variant in RYR2. Variants in RYR2 have not been linked to HCM. Other variants in RYR2 have been associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). Variants in this gene have also been associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), though this association is debated.

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