ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.5929G>A (p.Val1977Ile)

gnomAD frequency: 0.00001  dbSNP: rs786205741
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000170761 SCV000223316 likely benign not specified 2012-08-01 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001050965 SCV001215098 uncertain significance Long QT syndrome 2023-11-09 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1977 of the CACNA1C protein (p.Val1977Ile). This variant is present in population databases (rs786205741, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CACNA1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 190627). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CACNA1C protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV003362706 SCV004073043 uncertain significance Cardiovascular phenotype 2023-06-22 criteria provided, single submitter clinical testing The p.V1977I variant (also known as c.5929G>A), located in coding exon 46 of the CACNA1C gene, results from a G to A substitution at nucleotide position 5929. The valine at codon 1977 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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