A recurrent single-amino acid deletion (p.Glu500del) in the head domain of ß-cardiac myosin in two unrelated boys presenting with polyhydramnios, congenital axial stiffness and skeletal myopathy

Table 1 Comparison of all four patients in the literature with a mutation at MYH7-residue p.Glu500

Color-code for bottom rows: red = feature was present; green = feature was absent; white = feature was not investigated; HCM = hypertrophic cardiomyopathy; ASH = atrial septal hypertrophy; SCD = sudden cardiac death; N.A. = not available
^#Classification of the variant according to the recommendations of the ACMG (American College of Medical Genetics); ^#§ccording to ACMG criteria, the missense variant can be classified as likely pathogenic as it fulfils 2 moderate and ≥ 2 supporting criteria for pathogenicity, i.e. PM1 = well-established functional domain, PM2 = absent from controls, PP2 = missense variant in a gene that has a low rate of benign missense variation, PP3 = pathogenic computational verdict based on twelve pathogenic predictors and no benign predictions. ^§clinical classification as given in Walsh et al. 2017 on the basis of a single patient is: VUS favors pathogenic [13] (VUS = variant of uncertain significance). An entry in ClinVar (SCV002177799.1) classifies the variant as VUS according to Sherloc [14]

ISSN: 1750-1172