Figure 1:

Pathogenic variants in MYBPC1. (A) Schematic representation of the domain structure of sMyBP-C encoded by MYBPC1 and depiction of known (in blue) and novel (in red) pathogenic variants; Ig and FN-III domains are shown as white and grey rectangles, the Pro/Ala rich motif and the M-motif are illustrated as dark and light grey, thick, horizontal lines, and spliced sequences are depicted as colored, perpendicular lines. (B) Pedigrees and Sanger traces of the three families containing the novel pathogenic MYBPC1 variants. Individuals 1, 3 and 4 carry the p.Leu263Arg variant, which appeared de novo in individuals 1 and 4 belonging in two different families, and was inherited by individual 3 (daughter; proband) from individual 4 (father), while individual 2 belonging to a third unrelated family carries the de novo p.Leu259Pro variant. (C) Evolutionary conservation of L259 and L263 across orthologs from vertebrate species; conserved residues surrounding L259 and L263 within the M-motif are highlighted in yellow, while L259 and L263 are marked with red boxes; H.s. denotes Homo sapiens; M.m., Mus musculus; O.c., Oryctolagus cuniculus; B.t., Bos taurus; G.g., Gallus gallus; X.t., Xenopus tropicalis; D.r., Danio rerio.