Identification of recurrent MYH7 variant hypertrophic cardiomyopathy patients in Korea: a case series

Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous cardiac disorder often caused by variants in sarcomeric genes such as MYH7. The p.Tyr134His variant in MYH7 has previously been reported only once in a Korean HCM patient and was classified as a variant of uncertain significance (VUS), with no further supporting evidence available. This study adds to the literature by providing additional clinical and genetic evidence for this rare variant, suggesting a possible Korean-specific founder effect.

We identified eight unrelated Korean patients with HCM, all carrying the heterozygous MYH7 NM_000257.4:c.400T>C (p.Tyr134His) variant. These patients underwent exome sequencing across multiple clinical centers in South Korea. Clinical presentations varied from asymptomatic cases to those with arrhythmia, syncope, or structural changes such as asymmetric septal hypertrophy. No other pathogenic variants in known cardiomyopathy genes were identified in all eight patients. The variant was absent in major public and Korean population databases but present only in Korean HCM patients from our in-house cohort. In silico tools, including REVEL, AlphaMissense, and 3Cnet, consistently predicted deleterious effects.

Our findings provide clinical and population-level evidence supporting the pathogenicity of the p.Tyr134His variant in MYH7, potentially representing a rare Korean-specific founder mutation. However, as functional studies have not yet been performed, the pathogenic mechanism remains unconfirmed. Therefore, while current evidence remains of uncertain significance, further experimental validation may provide additional evidence to reclassify the variant as likely pathogenic.