Dysregulation of thick filament-based activation mechanisms appears to be the basis of many cardiomyopathies, including hypertrophic cardiomyopathy, which is hypothesized to be due to increased release of myosin heads from the sequestered off to on states and thereby increasing force-producing cross-bridges (Spudich, 2019; Nag and Trivedi, 2021), leading to hypercontractility and diastolic impairment. This evidence concerns the gene MYH14 and hypertrophic cardiomyopathy.