Variants in the KCNQ1 gene have been reported to cause autosomal dominant hypertrophic cardiomyopathy(HCM) based on case-level data alone in 2016. Previously, only 1 missense variant has been reported in an individual that presented with HCM and long QTc (LQTS) (PMID: 24183960). This individual also carried variants in two other genes associated with HCM. The re-curation of KCNQ1 presented 1 missense variant (c1781G>A, p.(Arg594Gln) in an individual with HCM and long QTc intervals (Cava et al., 2021 PMID: 33777698). This individual also carries a variant in TNNI3 (c.592C>G, p.Leu198Val). This variant in TNNI3 is considered likely pathogenic and segregated in individuals in the family presenting with hypertrophic cardiomyopathy. Variants in KCNQ1 have been shown to be pathogenic in individuals and families with Long QT. The current ClinGen Clinical Validity Framework is for Mendelian inheritance and does not support classifications for disease in which multiple genes may be contributory. At this time there is no clinical or experimental evidence to support association of KCNQ1 to HCM pathogenicity.
This curation was previously published by the Hypertrophic Cardiomyopathy GCEP in 2017 with a classification of No Known Disease Relationship. At this time, during recuration, the relationship of KCNQ1 with autosomal dominant hypertrophic cardiomyopathy has now been classified as DISPUTED by the Hereditary Cardiovascular Diseases GCEP as of April 13, 2022.
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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