2.1 Selection of human missense mutations.
By choosing from the default filter list in ClinVar web pagemissense as molecular consequence , we have made a preliminary selection of 308,326 entries. Then, we have refined our selection by applying the clinical significance filter for benign and pathogenic missense mutations obtaining respectively 25,579 and 22,153 items entries. From pathogenic missense mutations, we excluded 558 entries that were related to more than one mutations, often unlikely to occur, being associated with double or triple nucleotide changes between replaced amino acids. Thus, we have considered 21,595 ClinVar items with single missense mutations, which represent the content of our pathogenic missense mutation (PMM) data set. In the case of benign missense mutations, instead, all 25,579 were related to single mutations, being all these entries controlled with at least one star in the ClinVar nomenclature. Thus, all the 25,579 benign missense mutation (BMM) are single mutations entries and form the BMM data set.