SNTA1 encoded Alpha-1-syntrophin, a cytoskeletal protein thought to interact with the cardiac sodium channel. Candidate genes studies identified missense variants in this gene in patients with genotype-negative LQTS (PMIDs 18591664, 19684871). One of these variants, however, is now known to be present in ~1:150 individuals of European descent, making it an unlikely cause of a rare disease. Because of the candidate gene approach, lack of segregation or case-control data and paucity of additional genetic and experimental data, this gene-disease association was classified as disputed. Note: All LQTS genes were curated by 3 separate blinded teams. The evidence and scores reached by these 3 teams was reviewed by the LQTS Clinical Domain Working Group. The classification and summary presented here is the conclusion of this Working Group's analysis according to evidence teams' efforts. For a detailed discussion of this group's work and the scores of all 3 teams please see "Adler et al. An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome. Circulation 2020;141(6):418-428. doi: 10.1161/CIRCULATIONAHA.119.043132”
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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