Still, truncal PBRM1 mutations are observed in an additional ccRCC evolutionary subtype characterized by multiple driver clonal mutations in genes that include, in addition to PBRM1, BAP1, SETD2, or PTEN. These tumors have low ITH and high genomic instability and are associated with a rapid progression to multiple sites. The gene discussed is SETD2; the disease is nonpapillary renal cell carcinoma.