ClinVar Miner

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

gnomAD frequency: 0.00048  dbSNP: rs201492706
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Total submissions: 11
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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
Eurofins Ntd Llc (ga) RCV000079296 SCV000111166 uncertain significance not provided 2015-02-06 criteria provided, single submitter clinical testing
GeneDx RCV000079296 SCV000223310 benign not provided 2021-01-18 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 22840528, 20817017)
Invitae RCV001081791 SCV000259473 likely benign Long QT syndrome 2024-01-29 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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.
Ambry Genetics RCV002336232 SCV002641062 likely benign Cardiovascular phenotype 2018-06-28 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224137 SCV003919752 uncertain significance Timothy syndrome; Brugada syndrome 3; Long qt syndrome 8; Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures 2021-03-30 criteria provided, single submitter clinical testing CACNA1C NM_000719.6 exon 42 p.Ala1717Gly (c.5150C>G): This variant has not been reported in the literature but is present in 0.1% (41/34056) of Latino alleles, including 1 homozygote, in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs201492706). This variant is present in ClinVar, with several labs classifying this variant as Likely Benign (Variation ID:93411). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant suggests that this variant does not cause disease, but requires further evidence. Therefore this variant is classified as Likely Benign.
Dept of Medical Biology, Uskudar University RCV001081791 SCV004022092 uncertain significance Long QT syndrome 2024-01-08 criteria provided, single submitter research Criteria: BS1, PP2
CeGaT Center for Human Genetics Tuebingen RCV000079296 SCV004132349 benign not provided 2023-09-01 criteria provided, single submitter clinical testing CACNA1C: BS1, BS2
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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