The TNNT2 homozygous knockout model generated by TALENs showed hallmark features of cardiomyopathy, such as sarcomeric disarray and impaired intracellular Ca2+ cycling, while the heterozygous knockout did not show any structural or functional abnormalities suggesting that haploinsufficiency is unlikely to explain the pathogenesis of TNNT2-related cardiomyopathies. Here, TNNT2 is linked to cardiomyopathy.