KCNQ1 encodes the alpha subunit of the slowly activating delayed rectifier cardiac potassium channel (Iks). Bellocq et al. were the first to identify a rare KCNQ1 missense variant (p.Val180Leu ClinVar Variation ID# 3148) in a patient with SQTS (PMID 15159330). Subsequently, 9 other probands with SQTS were found to carry another variant (p.Val14Met, ClinVar Variation ID# 67072). Interestingly, all of these 9 cases presented with severe bradycardia in-utero or at birth and in 6 atrial fibrillation was also documented (PMIDs 24818999, 26279191, 16109388, 24380499, 25974115, 28491547). Importantly, in none of the p.Val14Met cases was cardiac arrest or SCD described. In fact, cardiac arrest was described only in the first case described by Bellocq et al. In 4 cases the p.Val14Met variant was demonstrated to be de-novo although paternity was not proven in all. In another 4 cases no other family members were diagnosed and in one family the father of the proband was identified with the p.Val14Met variant and demonstrated a mild phenotype. The fact that almost all genetic evidence was derived from a single variant led the Expert Panel to limit the classification of KCNQ1 as a SQTS-causing gene to “Strong”, despite evidence being reproducible over time.
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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