ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.10381A>G (p.Met3461Val) (rs147512481)

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Total submissions: 6
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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 RCV000171766 SCV000055288 likely benign not provided 2013-06-24 criteria provided, single submitter research
Invitae RCV001082739 SCV000637473 likely benign Catecholaminergic polymorphic ventricular tachycardia 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000620370 SCV000734909 uncertain significance Cardiovascular phenotype 2016-12-21 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
GeneDx RCV000171766 SCV000970916 likely benign not provided 2018-03-16 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.
Color RCV001180037 SCV001344885 likely benign Cardiomyopathy 2018-12-10 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001194069 SCV001363325 benign not specified 2019-10-15 criteria provided, single submitter clinical testing Variant summary: RYR2 c.10381A>G (p.Met3461Val) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00013 in 248876 control chromosomes, predominantly at a frequency of 0.0018 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 72 fold of the estimated maximal expected allele frequency for a pathogenic variant in RYR2 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.10381A>G has been reported in the literature in individuals with limited information (Ng_2013, Landstrom_2017). These reports do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. Three ClinVar submissions (evaluation after 2014) cite the variant twice as likely benign and once as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.

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