SETD2 is a tumor suppressor gene and the most somatic driver SETD2 mutations are truncating but the c.5218C > T (R1740W) somatic variant is listed five times (out of 2938 unique samples with mutations) entries in the Catalogue of Somatic Mutations in Cancer (COSMIC) database (accessed 5.01.2023) (the exact germline SETD2 LLS-associated loss of function mutations described here are not present in the COSMIC database but a somatic mutation producing a very similar truncated protein (p.Lys1486Argfs*29) to that in SETD2-LLS-P4 has been reported in a single renal cell carcinoma (42). This evidence concerns the gene SETD2 and neoplasm.