Hypertrophic cardiomyopathy (HCM) is a monogenic cardiovascular disorder that is caused mainly by mutations in sarcomeric contractile proteins such as cardiac troponin T (TNNT2). Becker et al. create a tnnt2 zebrafish morphant to study basic mechanisms of HCM pathology and to identify modifiers of the HCM phenotype. Their findings indicate that tnnt2 deficiency initiates cardiac defects at early developmental stages, including abnormalities in cardiomyocyte calcium handling. These findings suggest that the pathology of HCM might arise during development, before the onset of symptoms.