MYL2 and obesity due to melanocortin 4 receptor deficiency: The difference in penetrance in population versus family studies emphasizes the presence of defined and undefined genetic and environmental factors associated with greater risk of developing HCM, including ethnicity,23 the presence of multiple P/LP variants,24 obesity,25 and hypertension.26 For example, the penetrance of HCM in MYL3 carriers was 32%, contrasting with the 65% penetrance observed in MYL2 carriers, although both genes serve a similar molecular function.