The most commonly detected VHL mutation is called "712." It is associated with the development of tumors in many sites--in the eyes, kidneys, adrenal glands, brain, and spinal cord. The mutation involves a simple base change: thymine replaces cytosine at position 712 in the gene.

Another well-characterized mutation is "505." This mutation is associated with tumors in the eyes and adrenal glands (1). The tumors arise from cells that form blood vessels and from cells that secrete hormones. The 505 mutation involves a second simple switch that is the opposite of the switch that accounts for the "712" mutation. Normally the base thymine is at position 505, but in the altered genes a cytosine appears there instead. This small change affects the amino acid sequence of the tumor suppressor protein, replacing the tyrosine at position 169 with a histidine (10). Seventy percent of people with the 505 mutation develop clinical problems but the other 30% do not.