PMC8733160_01
Clinical manifestations in ECG and imaging. (A) ECG revealed CRBBB, abnormal double atrium, ventricular hypertrophy, first-degree atrioventricular block, and ST segment changes (lead I, aVL, and V3-V6 depression >0.05 mV). (B) Echocardiography indicated severe LVH. (C) Cardiac magnetic resonance imaging depicted hypertrophic left ventricular wall in both short axis and long axis views. CRBBB, complete right bundle branch block; ECG, electrocardiogram; LVH, left ventricular hypertrophy.
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Electrocardiography (ECG) revealed electrical axis deviation to the right, complete right bundle branch block (CRBBB), abnormal double atrium, ventricular hypertrophy, first-degree atrioventricular block, ST segment changes (lead I, aVL, and V3-V6 depression >0.05 mV) (Figure 1A). Echocardiography have been performed by the same echocardiographist to make the data comparable, and the echocardiography pre-ICD implantation indicated significant LVH and hypertrophic interventricular septum (19 mm, Z-score = 5.64) at the end of diastole with normal left ventricular systolic function (62-71.6%) (Figure 1B). Scattered flaky enhancement foci were evident in the myocardium, suggesting myocardial fibrosis (Figure 1C).
PMC8733160_02
Effects of MYH7 c.2723T>C mutation on molecular protein structure. (A) Ramachandran plots of MYH7 with and without p.L908P mutation. (B) SWISS-MODEL to predict the variant's wild-type and mutated protein crystal structures using 5tby.1.A template, and structural changes identified in the helix. (C,D) The mCSM tool used to predict protein stability revealed a decline in Gibbs free energy, indicating an unstable protein structure associated with this mutation. (E) Missense 3D analysis indicated that MYH7 p.L908P caused a structure clash.
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The capability of the protein structure was estimated using Ramachandran plots (Figure 2A). Ramachandran plots indicated that amino acid positions were altered (Figure 2A). Rebuilding molecular structure based on a 5tby.1.A templet resulted in residue changes between Leu and Pro at 908 (Figure 2B). Using SWISS-MODEL protein stability prediction tools, ensemble changes among all the coded amino acids exhibited significant variance (Figure 2C). Three types of calculation methods all demonstrated significant destabilizing change (mCSM, -1.571 Kcal/mol; DUET, -2.044 Kcal/mol; SDM -3.140 Kcal/mol; Figure 2D). Missense3D tool was also used to evaluate the molecular probity clash score. MYH7 p.L908P predicted obvious protein clash, with an elevated clash score > 18.00 (Figure 2E).
PMC8733160_03
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