The algorithms dNdScv, MutPanning, and MutSigCV identified 16 significantly mutated genes (q < 0.1 by any tool) (Fig. 1A and Additional file 7: Table S6), 13 of which are well-documented driver genes in melanoma and known to activate the MAP kinase (MAPK) pathway (BRAF, NRAS, NF1, KIT, SPRED1, and KRAS) or other pathways (PTEN, ATRX, CTNNB1, TP53, CDKN2A, SF3B1, and B2M). The gene discussed is SPRED1; the disease is melanoma.