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.