ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.275A>C (p.Gln92Pro)

gnomAD frequency: 0.00001  dbSNP: rs766650940
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000813007 SCV000953340 uncertain significance Long QT syndrome 2022-05-29 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 92 of the CACNA1C protein (p.Gln92Pro). This variant is present in population databases (rs766650940, gnomAD 0.009%). 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: 656558). 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: "Benign"; Align-GVGD: "Class C0"). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004768685 SCV005381694 uncertain significance not specified 2024-08-27 criteria provided, single submitter clinical testing Variant summary: CACNA1C c.275A>C (p.Gln92Pro) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 247558 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.275A>C in individuals affected with Timothy Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 656558). Based on the evidence outlined above, the variant was classified as uncertain significance.

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