Germline mutations were found in twenty VHL probands and their families, of whom 17 presented with a family history (15 from Brazil, one from Portugal, and one from Ecuador) . An intronic variant, c.340+7G>A, (reported as IVS1+7G>A in the paper) was found in 2 affected family members that both presented with with hemangioblastomas of the CNS. They were able to analyze the germline mutation linkage to disease in this family. The pathogenic nature of the variant was not confirmed at the mRNA level; however, the fact that this alteration was not detected in one unaffected first degree relative (after clinical and radiological screening) suggests that it may be associated with the disease. Additionally, the reported novel mutation were not represented in 120 alleles from normal subjects in the Brazilian population suggesting that these base changes are not common polymorphisms.