ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.6329dup (p.Glu2111fs) (rs771708175)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000454638 SCV000538551 uncertain significance not specified 2016-04-25 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: LOF not a known disease mechanism for CACNA1C ; ExAC: 2/57170 European chromosomes
Invitae RCV000477263 SCV000553027 uncertain significance Long QT syndrome 2019-10-21 criteria provided, single submitter clinical testing This sequence change inserts 1 nucleotide in exon 47 of the CACNA1C mRNA (c.6329dupG), causing a frameshift at codon 2111. This creates a premature translational stop signal in the last exon of the CACNA1C mRNA (p.Glu2111Argfs*15). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 14 amino acids of the CACNA1C protein. This variant is present in population databases (rs771708175, ExAC 0.003%) but has not been reported in the literature in individuals with a CACNA1C-related disease. ClinVar contains an entry for this variant (Variation ID: 190695). Experimental studies have not been reported for this truncating variant and it is currently unknown if the last 14 amino acids of the CACNA1C protein are critical for its function. In summary, this variant is a rare deletion with uncertain impact on protein function. Therefore, it has been classified as a Variant of Uncertain Significance.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000757054 SCV000885137 uncertain significance not provided 2017-11-21 criteria provided, single submitter clinical testing The p.Glu2111fs variant (rs771708175) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant creates a frameshift in the CACNA1C protein at codon 2111 in exon 47/47 which results in a premature termination codon and is predicted to result in a truncated protein product. Truncating variants have not been reported as a causative mechanism of disease in the CACNA1C gene. This variant is listed in the Genome Aggregation Database (gnomAD) with an overall population frequency of 0.002 percent (identified on 4 out of 241,582 chromosomes) and has been reported to the ClinVar database as a variant of uncertain significance (Variation ID: 190695). Altogether, there is not enough evidence to classify the p.Glu2111fs variant with certainty.

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