Variant filtering and prioritization
The variants identified by whole-exome sequencing where subsequently filtered for the selection of those variants that were: 1) shared by the cancer-affected family members sequenced; 2) carried in heterozygosis; 3) coding (frameshift, inframe, nonsense, splicing or missense) and affecting autosomes; 4) rare (minor allele frequency (MAF)≤0.01 in the general population) and not present in 3 or more families; 5) predicted to be damaging by least 4 out of 5 in silico tools for missense variants and 2 out of 2 for inframe variants, or predicted to alter splicing for splice region variants; and 6) absent in a healthy elderly relative sequenced (when applicable). Finally, the filtered variants were prioritized based on the relevance of the gene and the location of the variant in the protein structure, allowing the selection of a list of candidate variants.