ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.5731G>C (p.Gly1911Arg) (rs374528680)

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Total submissions: 7
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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 RCV000171619 SCV000055190 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000171619 SCV000230669 uncertain significance not provided 2015-02-02 criteria provided, single submitter clinical testing
Invitae RCV000226828 SCV000285599 uncertain significance Long QT syndrome 2018-11-28 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 1911 of the CACNA1C protein (p.Gly1911Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs374528680, ExAC 0.08%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811) This variant has been reported in the literature in an individual affected with Timothy syndrome, an infant with sudden unexplained death at the age of 1 month, and in an adult with aborted cardiac arrest and a Brugada pattern on ECG (PMID: 25184293, 26230511). This variant is also described as c.5875G>C (p.Gly1959Arg) in the literature.  ClinVar contains an entry for this variant (Variation ID: 191427). Experimental studies have shown that this missense change produces a gain of function of the channel by decreasing its voltage dependent inactivation (PMID: 25184293). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000515185 SCV000611378 uncertain significance Timothy syndrome; Brugada syndrome 3 2017-05-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000171619 SCV000697555 uncertain significance not provided 2016-12-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV000617712 SCV000737990 uncertain significance Cardiovascular phenotype 2017-04-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852446 SCV000995138 uncertain significance Cardiomyopathy 2018-02-11 criteria provided, single submitter clinical testing

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