Phenotypic and clinical evaluation of hypertrophic cardiomyopathy caused by the deep intronic variant MYBPC3:c.2308+227G>A

Abstract Introduction Deep intronic variants can be the cause of hypertrophic cardiomyopathy (HCM), although these regions of the genome are not always sequenced in genetic studies. It is unknown if there are differences in phenotypic expressivity and prognosis compared to other forms of HCM. Objective to describe the phenotypic and clinical characteristics of a cohort of probands with HCM due to the variant MYBPC3:c.2308+227G>A and compare whether there are differences with other HCM groups. Methods Retrospective observational study of the clinical and imaging data of patients with HCM evaluated in a reference center for Inherited Cardiovascular Disease. Probands carrying the MYBPC3:c.2308+227G>A variant, other pathogenic or likely pathogenic variants in MYBPC3 and those with a negative genotype (NGS sequencing) were included. Results 151 probands with HCM (70% males; age of diagnosis 56±14) were included, 26 carrying MYBPC3:c.2308+227G>A (figure). No significant differences were found between the three groups in terms of baseline characteristics, phenotypic features or risk profile. In the survival curves, the subgroup with the variant had a earlier tendency to events, particularly for heart failure (figure). Conclusions HCM associated with MYBPC3:c.2308+227G>A variant does not have differential characteristics in its phenotypic and clinical expression, having a similar prognosis to other HCM in our cohort.