ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.5150C>G (p.Ala1717Gly) (rs201492706)

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Total submissions: 8
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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 RCV000079296 SCV000050758 likely benign not provided 2013-06-24 criteria provided, single submitter research
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000079296 SCV000111166 uncertain significance not provided 2015-02-06 criteria provided, single submitter clinical testing
GeneDx RCV000212340 SCV000223310 likely benign not specified 2017-09-07 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 RCV001081791 SCV000259473 likely benign Long QT syndrome 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000343666 SCV000377891 likely benign Timothy syndrome 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000212340 SCV000697549 likely benign not specified 2019-03-18 criteria provided, single submitter clinical testing Variant summary: CACNA1C c.5150C>G (p.Ala1717Gly) results in a non-conservative amino acid change located in the Voltage-gated calcium channel subunit alpha, C-terminal of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00076 in 272838 control chromosomes in the gnomAD database, including 1 homozygotes. The observed variant frequency is approximately 75.87 fold of the estimated maximal expected allele frequency for a pathogenic variant in CACNA1C causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. c.5150C>G has been reported in the literature in individuals affected with cardiac phenotypes (Burashnikov_2010, Crotti_2012, Forleo_2017, Kostareva_2016, Wemhoner_2015) however without strong evidence for causality. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as likely benign.
Blueprint Genetics RCV000157124 SCV000206847 uncertain significance Restrictive cardiomyopathy; Long QT syndrome 2014-06-24 no assertion criteria provided clinical testing
CSER _CC_NCGL, University of Washington RCV000288792 SCV000503535 likely benign Brugada syndrome 2016-08-01 no assertion criteria provided research Found in patient having exome sequencing for an unrelated indication. No known history of Brugada syndrome.

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