SCN5A and dilated cardiomyopathy: Three mutations, targeting the gating charges on the S4 of Nav1.5 VSD I (R219H, R222Q, and R225W; R1, R2, and R3, respectively), and a fourth mutation targeting R3 on S4 of Nav1.5 VSD II (R814W), all found in unrelated patients suffering from ventricular arrhythmias and dilated cardiomyopathy (Gosselin-Badaroudine et al., 2012b; Moreau et al., 2015b; Jiang et al., 2018), were capable of generating gating pore currents when expressed in heterologous systems.