In silico studies
The MAF of the identified variants in the general population was checked in three different databases: 1000 Genomes Project, Exome Variant Server and GnomAD. On the other hand, the in silico tools used for the damage prediction were SIFT, PolyPhen, Condel, MutationTaster and PROVEAN for missense variants, and only the last two for inframe variants. This was done with the help of Ensembl’s Variant Effect Predictor tool. Splicing alterations were predicted by the Human Splicing Finder. For variant prioritization, all genes affected by filtered variants were thoroughly examined with UniProt, OMIM, Reactome, PathCards, Pubmed, STRING, SMART and cBioPortal’s MutationMapper. The 3D structure of the genes affected by these variants was simulated by SWISS-MODEL in order to visualize the effects of the mutations on the protein structure.