Although protein-coding regions span only about 1% of the genome, 15 out of 50 (30%) of the most frequently mutated sites were well-studied hotspots in cancer genes (KRAS, BRAF, PIK3CA, TP53 and IDH1) (Fig. 1a, Extended Data Fig. 1b), along with the two canonical TERT promoter hotspots6,7. The gene discussed is TP53; the disease is cancer.