Genetic engineering of heterozygous and homozygous gain-of-function RBM20 p.R636S allelic mutants by transcription activator-like effector nucleases and CRISPR-Cas9 gene editing yielded iPSC-CMs that exhibited electrophysiological and contractile abnormalities reminiscent of DCM observed in patients. This evidence concerns the gene RBM20 and familial dilated cardiomyopathy.