ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.3500T>C (p.Val1167Ala)

dbSNP: rs2153440081
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001765427 SCV001998101 likely pathogenic not provided 2023-06-21 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34163037)
Mendelics RCV002246476 SCV002518629 pathogenic Timothy syndrome 2022-05-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003647853 SCV004489946 pathogenic Long QT syndrome 2023-12-19 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1167 of the CACNA1C protein (p.Val1167Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Clinical features of Timothy syndrome (PMID: 34163037). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 1309258). 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 expected to disrupt CACNA1C protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

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