Selected germline VHL variants with isolated polycythemia

Polycythemia due to a pathogenic variant in VHL is also referred to as familial erythrocytosis 2 (ECYT2) or Chuvash polycythemia (for a region in Russia where this was first identified); however, these variants are not restricted to individuals from Russia. The variants listed in this table do not cause VHL disease.

• Chuvash polycythemia is autosomal recessive, caused by specific biallelic (homozygous or compound heterozygous) pathogenic variants in VHL. In contrast, VHL disease, a hereditary cancer syndrome, is autosomal dominant.
• Other variants not included in this table may be associated with isolated polycythemia. Consult an updated database, VHL expert, or genetics professional for questions.
• These alleles are generally point mutations that cause reduced but not absent VHL function.
• Individuals with one or more pathogenic variants in VHL should speak with a genetic counselor or an expert in VHL disease to determine their risk for VHL disease, which requires surveillance for several types of tumors.
• Pathogenic variants in VHL have been estimated to account for approximately 50% of hereditary erythrocytosis with high EPO levels; pathogenic variants in other genes are thought to account for the remainder.
• Refer to UpToDate for management of VHL disease, Chuvash polycythemia, and other heritable polycythemia syndromes.