Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease, which can cause arrhythmias and heart failure. It has been proposed that HCM clinical hypercontractility derives from mutations that destabilise the myosin energy-conserving state SRX, causing myosin release. Mavacamten, the first drug specifically developed to target HCM pathophysiology, was shown to reverse this by sequestering myosins in SRX. However, a deeper mechanistic understanding of Mavacamten action and its safety and efficacy in specific HCM subgroups is needed to guide effective and safe patient-specific therapy. Here we extend a human cardiomyocyte electromechanical model to include representation of myosin sequestration and release from SRX, and we investigate how HCM- and Mavacamten-induced SRX changes alter cellular contractility. A simulation study is conducted to mechanistically unravel how Mavacamten restores tension generation in the HCM-causing β-myosin heavy chain mutation MYH7R403Q/+. From the baseline model, we constructed a control and MYH7R403Q/+ population of 348 cardiomyocytes models, quantified changes in tension generation at baseline and under Mavacamten and compared results to experimental evidence. Our model of sequestration and release of myosin by SRX allowed to describe changes in tension by crossbridges availability. It replicated the tension reduction under Mavacamten in control cardiomyocytes, and the tension increase under MYH7R403Q/+, as experimentally observed. In our population of MYH7R403Q/+ models, hypercontractility is caused by larger crossbridge cycling due to myosin release from SRX. However, diastolic dysfunction can only be recapitulated by also considering a crossbridge-based contribution to thin filament activation, slowing calcium release from troponin. Mavacamten rescued the hypercontractile phenotype and the associated impaired relaxation of simulated MYH7R403Q/+ cardiomyocytes, in agreement with experiments. We demonstrate that Mavacamten is highly effective in correcting HCM abnormalities caused by mutations that destabilise SRX, but residual traits of specific genotypes may remain untreated if originated through different pathways than SRX destabilisation.