Supplementary Material for: A Novel <b><i>SCN5A</i></b> Variant Associated with Abnormal Repolarization, Atrial Fibrillation, and Reversible Cardiomyopathy

A variety of life-threating arrhythmias are caused by mutations in the cardiac voltage-gated sodium channel encoded by the<i> SCN5A</i> gene. In this study, we report a novel loss-of-function <i>SCN5A</i> variant, p.Ile1343Val (c.4027A>G), identified in a 42-year-old proband who presented with an unusual ECG with abnormal repolarization with biphasic T-waves in anteroseptal leads, persistent atrial fibrillation (AF), intermittent left bundle branch block (LBBB), and reversible cardiomyopathy. The patient did not meet the diagnostic criteria for Brugada syndrome, long QT syndrome, or any other known <i>SCN5A</i>-associated phenotype. Characterization of the biophysical properties of the variant by in vitro<i></i> patch clamp experiments revealed a reduced Na<sup>+</sup> current with no effect on the inactivation kinetics of the channel. This loss-of-function of Na<sup>+</sup> current could explain the intermittent LBBB as well as the AF. In conclusion, we describe a unique combination of electrical and structural abnormalities associated with a novel <i>SCN5A</i> variant. Our findings broaden the spectrum of cardiac phenotypes associated with <i>SCN5A</i> channelopathy, underlining the complex clinical manifestations of genetic variations within this gene.



CC BY 4.0