FBXW7 is a tumor suppressor gene responsible for the degradation of several proto-oncogenes, and is mutated in several tumors including colorectal, liver, bladders and ovarian cancers. mTOR is one of the substrates of FBXW7-mediated protein degradation, and loss of function of FBXW7 increases the levels of total and activated mTOR. FBXW7 loss of function mutations have been described in many types of adenocarcinoma including colon, bladder and lung. FBXW7 mutations are present in approximately 7% of urothelial carcinomas. Preclinical data have suggested that inactivating mutations of FBXW7 could predict sensitivity to the mTOR inhibitor rapamycin. However, this particular variant (H500Y) has not been characterized in the scientific literature. Therefore, the effect on protein function is unknown. Clinical correlation is recommended.