CACNA1C encodes for the alpha-1c subunit of the voltage-dependent L-type calcium channel which is important for the development of the action potential in human cardiomyocytes. Genetic variants in this gene have been identified in 5 probands with suggested SQTS phenotype. Three of these probands, however, had Brugada syndrome with a relatively short QT interval (PMIDs 17224476, 20817017) and one had hypertrophic cardiomyopathy without a convincing SQTS phenotype (PMID 28427417). Accordingly, the SQTS Gene Curation Expert Panel decided these patients did not have an isolated SQTS phenotype and the genetic evidence derived from these cases should not be scored toward relationship of CACNA1C with SQTS. The final proband was identified as having a de novo variant (PMID 24291113), however, the gnomAD MAF was regarded as too high for a rare condition such as SQTS and there was no other evidence supporting this variant’s impact.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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