ClinVar Miner

Submissions for variant NM_001167623.2(CACNA1C):c.1204G>A (p.Gly402Ser)

dbSNP: rs587782933
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000170768 SCV000223323 pathogenic not provided 2023-05-08 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect as channel inactivation was reduced, leading to maintained depolarizing L-type calcium currents (Splawski et al., 2005); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 29032884, 21685391, 23979604, 28807990, 28341588, 26822303, 15863612, 31408100, 25691416, 24773605)
Labcorp Genetics (formerly Invitae), Labcorp RCV000805941 SCV000945916 pathogenic Long QT syndrome 2023-12-14 criteria provided, single submitter clinical testing The CACNA1C gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_001129840.1, and corresponds to NM_000719.6:c.1114-316G>A in the primary transcript. This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 402 of the CACNA1C protein (p.Gly402Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with atypical Timothy syndrome (TS2) (PMID: 15863612, 23979604, 24773605, 25691416). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 155775). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this missense change affects CACNA1C function (PMID: 15863612, 21685391, 26822303). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003333028 SCV004041210 pathogenic Long qt syndrome 8 2023-05-25 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000143870 SCV000188738 likely pathogenic Ventricular fibrillation, paroxysmal familial, type 1 2013-11-20 no assertion criteria provided clinical testing

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