• Test Code:
  • Department:
  • Test Synonyms:
    VHL full gene sequencingVon Hippel-Lindau Disease sequencing
  • CPT Code(s):

von Hippel-Lindau (VHL) disease is a rare autosomal-dominant cancer syndrome caused by mutations in the VHL gene.  This disease is most commonly characterized by hemangioblastomas of the brain, spinal cord and retina; pheochromocytomas and renal cell carcinomas.  Point mutations and small insertions/deletions account for approximately 72%, while entire exon and gene deletions account for approximately 28% of the identified mutations.  In addition to VHL, mutations in the VHL gene also cause VHL-associated polycythemia (previously known as Chuvash type polycythemia).

Reasons for Referral:

  • Identification of inherited genetic defects in the VHL gene in patients with a clinical diagnosis of VHL disease or VHL-associated polycythemia.
  • Confirmation of a suspected diagnosis with a positive family history of VHL disease when a familial mutation is known.
  • Predispositional testing for asymptomatic family members with a positive family history of VHL.


Sequencing can be performed by either Sanger Sequencing or Next-Generation Sequencing.

Sanger Sequencing: Sequencing of VHL is carried out by amplification of all exons and intron/exon boundaries followed by bi-directional Sanger sequencing. The sensitivity of full gene sequencing is estimated to be approximately 99% for single nucleotide substitutions and small insertions/deletions. All nucleotide changes are analyzed within the context of current databases and literature to predict pathogenicity.

NGS: Next generation sequencing will analyze the exons or coding regions of VHL using Illumina NextSeq 500 technology. Samples are prepared using hybridization probes to enrich exonic regions. Promoter, intronic, etc. regions are not assessed on our assay, but may contain variants that impact gene function.

Test reporting follows the ACMG Standards & Guidelines for Clinical Genetics Laboratories, Ultra-Rare Disorders Guidelines, and Interpretation of Sequence Variants Guidelines.

Specimen Requirements:

Blood:  EDTA or ACD (Solution A or B):

  • Adult: 5 mL
  • Child: 5 mL
  • Infant: 2-3 mL

DNA: 10µg at a minimum of 100ng/µL

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):


Turn Around Time:

14-21 days

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cold, but not frozen. 
  • Ship via overnight express, using the FedEx priority overnight label provided. 
  • Contact Client Services for shipping kits and instructions at (855) 535-1522.


  1. Maher ER et al. von Hippel-Lindau disease: A clinical and scientific review. European Journal of Human Genetics 2011;19:617-623.
  2. Banks R et al. Genetic and epigenetic analysis of von Hippel-Lindau (VHL) gene alterations and relationship with clinical variables in sporadic renal cancer. Cancer Res 2006;66:2000-2011.
  3. Stolle C et al. Improved detection of germline mutations in the von Hippel-Lindau tumor suppressor gene. Human Mutation 1998;12:417-423.

Additional Info:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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