The pathogenicity of these variants is supported by several lines of evidence, including the well-established pathogenicity of the BRAF, KRAS, and NRAS variants in other disorders and tissues, the mosaic occurrence of these variants in the lesions and their absence in peripheral blood, and the existence of a hotspot of MAP2K1 variants in the Catalogue Of Somatic Mutations In Cancer (COSMIC) database (http://cancer.sanger.ac.uk/cosmic), comprising 65 tumor variants from F53 to E62. This evidence concerns the gene NRAS and cancer.