ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.2T>C (p.Met1Thr)

gnomAD frequency: 0.00001  dbSNP: rs761378545
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000170850 SCV000223405 uncertain significance not provided 2015-12-07 criteria provided, single submitter clinical testing p.Met1? (ATG>ACG): c.2 T>C in exon 1 of the CACNA1C gene (NM_000719.6). The c.2 T>C variant has not been published as a mutation or reported as a benign polymorphism to our knowledge. This sequence variant alters the initiator Methionine residue and the resultant protein could be described as p.Met1?" using a question mark to signify that it is not known if the loss of Met1 means that all protein translation is completely prevented or if an abnormal protein is produced using an alternate Met. The c.2 T>C variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The variant is found in ARRHYTHMIA panel(s)."
Invitae RCV000528382 SCV000627528 uncertain significance Long QT syndrome 2023-07-03 criteria provided, single submitter clinical testing This variant is present in population databases (rs761378545, gnomAD 0.004%). 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. ClinVar contains an entry for this variant (Variation ID: 190710). This variant has not been reported in the literature in individuals affected with CACNA1C-related conditions. This sequence change affects the initiator methionine of the CACNA1C mRNA. The next in-frame methionine is located at codon 8.
Fulgent Genetics, Fulgent Genetics RCV002478534 SCV000896280 uncertain significance Timothy syndrome; Brugada syndrome 3; Long qt syndrome 8 2021-10-16 criteria provided, single submitter clinical testing
AiLife Diagnostics, AiLife Diagnostics RCV000170850 SCV002501225 uncertain significance not provided 2022-01-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV003165345 SCV003896169 likely benign Cardiovascular phenotype 2023-01-30 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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