Clinical and Translational Medicine

Graphical Abstract SCN5A variant (c.3148G>A/p.Ala1050Thr) causes loss-of-function of sodium channels in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from BrS patient. SCN5A variant (c.3148G>A/p.Ala1050Thr) increases the channel sensitivity to hyperthermia and LPS challenge in hiPSC-CMs from BrS patient. Autophagy and PKA pathway mediate the effect of LPS and hyperthermia on hiPSC-CMs from BrS patient with SCN5A variant (c.3148G>A/p.Ala1050Thr), respectively.