Heterozygous germline LoF variants in VHL are associated with rare Mendelian diseases such as von Hippel-Lindau syndrome (OMIM 193300), which is a cancer susceptibility syndrome characterized by vascular anomalies such as retinal, pulmonary, liver and adrenal hemangiomas as well as the clear cell type of RCC. This evidence concerns the gene VHL and renal cell carcinoma.