NGS data validated by Sanger sequencing reveal a puzzling small deletion of MYBPC3 gene associated with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) has a special place among genetic cardiomyopathies, being one of the main causes of sudden death in young patients, mainly in performance athletes. Herein we report a deletion in the myosin binding protein C (MYBPC3) gene identified in a female patient affected by HCM. The mutation was initially pinpointed in an NGS screening, then it was confirmed by Sanger sequencing with original primers. Bioinformatics analysis revealed a deletion previously reported as c.2441_2443delAGA, but the precise breakpoints mapping appears to be difficult to conclude. Since alternative three nucleotides deletions unambiguously result in a net Lysine missing from a specific poly-Lysine protein domain, the absolute mapping of the mutation is yet elusive, an aspect which should be considered when reporting the genomic coordinates of this deletion.