A novel functional variant residing outside the SCN5A-encoded Nav1.5 voltage-sensing domain causes multifocal ectopic Purkinje-related premature contractions

Abstract

Pathogenic variants in the SCN5A-encoded pore-forming α-subunit of the Nav1.5 voltage-gated cardiac sodium channel are associated with primary arrhythmia syndromes including type 3 long QT syndrome (LQT3; Nav1.5 gain-of-function), Brugada syndrome (BrS; Nav1.5 loss-of-function), early-onset atrial fibrillation (AF; Nav1.5 loss- and gain-of-function), primary cardiac conduction disease (Nav1.5 loss-of-function), dilated cardiomyopathy (DCM; Nav1.5 loss- and gain-of-function), and overlap syndromes, whereby the clinical hallmark(s) of more than 1 disorder is observed with the same patient and/or family.