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Missense mutations in myosin heavy chain 7 (<i>MYH7</i>) are a common cause of hypertrophic cardiomyopathy (HCM), but the molecular mechanisms underlying <i>MYH7</i>-based HCM remain unclear. In this work, we generated cardiomyocytes derived from isogenic human induced pluripotent stem cells to model the heterozygous pathogenic <i>MYH7</i> missense variant, E848G, which is associated with left ventricular hypertrophy and adult-onset systolic dysfunction. <i>MYH7</i>^E848G/+ increased cardiomyocyte size and reduced the maximum twitch forces of engineered heart tissue, consistent with the systolic dysfunction in <i>MYH7</i>^E848G/+ HCM patients. Interestingly, <i>MYH7</i>^E848G/+ cardiomyocytes more frequently underwent apoptosis that was associated with increased p53 activity relative to controls. However, genetic ablation of <i>TP53</i> did not rescue cardiomyocyte survival or restore engineered heart tissue twitch force, indicating <i>MYH7</i>^E848G/+ cardiomyocyte apoptosis and contractile dysfunction are p53-independent. Overall, our findings suggest that cardiomyocyte apoptosis is associated with the <i>MYH7</i>^E848G/+ HCM phenotype in vitro and that future efforts to target p53-independent cell death pathways may be beneficial for the treatment of HCM patients with systolic dysfunction.