ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.4216G>A (p.Val1406Met)

dbSNP: rs753204879
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000170810 SCV000223365 uncertain significance not provided 2013-11-08 criteria provided, single submitter clinical testing p.Val1406Met (GTG>ATG): c.4216 G>A in exon 34 of the CACNA1C gene (NM_000719.6). The Val1406Met variant in the CACNA1C gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Val1406Met results in a conservative amino acid substitution of one non-polar amino acid for another at a position that is conserved across species. In silico analysis predicts Val1406Met is damaging to the protein structure/function. The Val1406Met variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, no other disease-causing mutations have been reported in surrounding residues of the CACNA1C protein, indicating this region may be tolerant of change. With the clinical and molecular information available at this time, we cannot definitively determine if Val1406Met is a disease-causing mutation or a rare benign variant. The variant is found in LQT panel(s).
Invitae RCV002517638 SCV002939869 uncertain significance Long QT syndrome 2022-06-03 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 190672). This variant has not been reported in the literature in individuals affected with CACNA1C-related conditions. This variant is present in population databases (rs753204879, gnomAD 0.0009%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1406 of the CACNA1C protein (p.Val1406Met).

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