Spatial and Functional Distribution of <i>MYBPC3</i> Pathogenic Variants and Clinical Outcomes in Patients With Hypertrophic Cardiomyopathy

Truncating variants account for 91% of <i>MYBPC3</i> pathogenic variants and cause similar clinical severity and outcomes regardless of location, consistent with locus-independent loss-of-function. Nontruncating <i>MYBPC3</i> pathogenic variants are regionally clustered, and a subset also cause loss of function through failure of myofilament incorporation and rapid degradation. Cardiac morphology and clinical outcomes are similar in patients with truncating versus nontruncating variants.