These results constitute the first analysis of the MYBPC3 (c.1224-52G>A, IVS13-52G>A) and SMYD1 (c.302A>G; p.Asn101Ser) variants in human tissue, functionally link genetic variations to cardiomyocyte dysfunction and provide key biological insights into the development of cardiomyopathies in pediatric patients. Here, SMYD1 is linked to cardiomyopathy.