A novel variant of KCNQ1 gene and pathogenicity prediction in a family with long QT syndrome type 1

Abstract

Abstract A novel heterozygous missense variant of KCNQ1 was identified in a family exhibiting LQTS with complete penetrance and its pathogenicity was predicted through multiple prediction software programs and 3D model analysis. The pathogenicity of the variant was predicted for its effect on a 3D model of KCNQ1, and in-depth functional analysis was performed for mechanistic speculation. We demonstrated that this variant, which is located in the conserved hot spot domain, was evaluated as likely pathogenic. In silico prediction indicated that the variation was involved in the process of channel closing/opening. This study reports a novel variation in KCNQ1, provides supportive evidence for pathogenicity prediction and enhances variant interpretation for patients with LQTS.