To demonstrate the ability of the oligonucleotide-directed mutagenesis screen to distinguish pathogenic MSH6 mutations from polymorphisms, a proof of principle study was performed with MSH6 variants G1139S and L1087R that were previously proven to be pathogenic and not pathogenic, respectively [25], as well as all classified pathogenic and not pathogenic missense variants described in the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) colon cancer variant database (http://insight-group.org/). Here, MSH6 is linked to colonic neoplasm.