ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.2630A>C (p.His877Pro) (rs561321743)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000176374 SCV000228022 likely benign not specified 2015-04-20 criteria provided, single submitter clinical testing
GeneDx RCV000176374 SCV000531175 likely benign not specified 2017-12-06 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.
Invitae RCV000470020 SCV000554607 benign Catecholaminergic polymorphic ventricular tachycardia 2019-12-31 criteria provided, single submitter clinical testing
Color RCV000771846 SCV000904560 benign Cardiomyopathy 2018-10-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000176374 SCV000920170 benign not specified 2018-11-05 criteria provided, single submitter clinical testing Variant summary: RYR2 c.2630A>C (p.His877Pro) results in a non-conservative amino acid change located in the Ryanodine receptor Ryr domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00071 in 276002 control chromosomes, predominantly within the Latino subpopulation at a frequency of 0.0055 in the gnomAD database. The observed variant frequency within Latino control individuals is approximately 92-fold above the estimated maximal expected allele frequency for a pathogenic variant in RYR2 causing Arrhythmia phenotype (6e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. To our knowledge, no occurrence of c.2630A>C in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and all classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852596 SCV000995298 likely benign Hypertrophic cardiomyopathy 2018-12-24 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000157448 SCV000207192 uncertain significance Primary familial hypertrophic cardiomyopathy 2014-10-07 no assertion criteria provided clinical testing

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