This report is one of only a few to describe a gene-targeted knock-in murine models of human mutations in TNNT2 leading to DCM, and to describe the consequences of the mutation on gene dosage, sex-dependent survival, molecular remodeling pathways, electrophysiological function, and Ca2+ sensitivity, transients, and homeostasis. This evidence concerns the gene TNNT2 and familial dilated cardiomyopathy.