Case Report: Genomic and clinical insights into MYBPC3-related hypertrophic cardiomyopathy in Ecuadorian patients: implications for sudden cardiac death risk

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and a leading cause of sudden cardiac death (SCD) in young adults and athletes. It exhibits marked clinical variability, which may be influenced by genetic background and environmental factors. Although <i>MYBPC3</i> is the most frequently implicated gene, data from Latin American and admixed populations remain scarce. In this study, we describe three unrelated Ecuadorian patients with clinically diagnosed HCM who harbored <i>MYBPC3</i> variants. Two patients carried likely pathogenic mutations (p.Glu258Lys and p.His875Profs*8), while novel missense variants (p.Ala536Pro and p.Thr274Met) were identified as variants of uncertain significance (VUS). Additional variants were detected in <i>TTN</i>, <i>MYLK2</i>, <i>RYR1</i>, <i>SDHA</i>, <i>APOB</i>, and <i>JPH2</i>, but given their classification as VUS or a lack of association with HCM, they are described only as incidental findings. An ancestry analysis revealed heterogeneous contributions of Native American, European, and African backgrounds, reflecting the admixed composition of the Ecuadorian population. This case series underscores the phenotypic heterogeneity of HCM, even among patients with <i>MYBPC3</i> variants, and highlights the importance of genomic testing in underrepresented populations to improve diagnosis, family screening, and SCD risk stratification.