Figure 1

Identification of AMBRA1 Q30R as a possible candidate germline variant using whole exome sequencing data of CS patients. (A) Pedigree of CS family comprising three affected (CS1, CS2, CS3) and two unaffected individuals. (B) Schematic representation of variant filtering and prioritization performed on WES data of the 3 CS probands and 2 unaffected family members. (C) In silico pathogenicity prediction and conservation score of 18 CS-specific variants. (D) Schematic representation of the AMBRA1 protein showing WD domains and CS variants Q30R locating near the WD40 (Tryptophan-Aspartic Acid repeats) domain and R1195S locating at the C-terminal region. Clustal-W2 Multiple sequence alignments at the bottom showed evolutionary conservation of the affected residues (highlighted in red) among species. The symbol * (asterisk) below the multiple sequence alignment indicates positions with a single, fully conserved residue; the symbol: (colon) indicates conservation between groups of strongly similar properties and the symbol. (period) indicates conservation between groups of weakly similar properties.