ClinVar Miner

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

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Total submissions: 8
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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 RCV001697153 SCV000531175 likely benign not provided 2020-02-13 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28404607)
Invitae RCV000470020 SCV000554607 benign Catecholaminergic polymorphic ventricular tachycardia 2020-12-04 criteria provided, single submitter clinical testing
Color Health, Inc RCV000771846 SCV000904560 benign Cardiomyopathy 2018-10-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001289827 SCV001477822 likely benign none provided 2019-08-01 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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