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Von Hippel-Lindau Disease via VHL Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
VHL 81404 81404,81403 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7523VHL81404 81404,81403 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Yuan Xue, PhD

Clinical Features and Genetics

Clinical Features

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that results in a variety of tumors, including retinal and central nervous system hemangioblastomas (most commonly), clear cell renal carcinomas, pheochromocytomas, pancreatic islet tumors, and endolymphatic sac tumors (Maher et al. Eur J Hum Genet 19(6):617-23, 2011). The presence of one of these tumors and a family history of VHL confirms a clinical diagnosis of VHL disease. The tumors presented in VHL can all appear sporadically in the general population; however, for a clinical diagnosis of VHL without a family history, two tumors common for VHL are required. Approximately 80% of VHL cases are inherited from an affected parent and 20% of cases are de novo. The age of malignant presentation for several tumors occurs earlier in VHL disease than sporadic cases (e.g., 29 vs. 48 years for cerebellar hemangioblastoma and 44.8 vs. 61.8 years for renal cell carcinoma; Maher et al. J Med Genet 27: 311–314, 1990). VHL disease occurs in approximately 1 in 36,000 livebirths.


Von Hippel-Lindau disease is caused by variants in the VHL gene, which is a tumor suppressor. Inactivation of both alleles at the cellular level results in abnormal activation of genes involved in hypoxia. VHL disease is inherited in an autosomal dominant manner and presents variable expressivity and age-dependent penetrance (Maher et al. Eur J Hum Genet 19(6):617-23, 2011). Genotype-phenotype correlations exist for VHL disease. For example, in families with truncating variants or exon deletions, pheochromocytomas are infrequent. There is allelic heterogeneity throughout the VHL gene; however, some variants have been described more frequently in some families (e.g., c.481C>T, c.499C>T, c.500G>A) . In addition, genetic modifiers have been described that influence tumor development (Frantzen et al. GeneReviews. 2012).

Clinical Sensitivity - Sequencing with CNV PG-Select

Genetic testing for VHL variants in patients with VHL disease achieves a molecular diagnosis in 90-100% of patients. Parental mosaicism has been reported (Sgambati et al. J Hum Genet 66:84–91, 2000). Approximately 89% of variants will be detected using sequencing. Approximately 11% of variants result from gross deletions and duplications (Nordstrom-O'Brien, Hum Mutat 31:521–37, 2010).

Testing Strategy

This test provides full coverage of all coding exons of the VHL gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Individuals with or without a family history of VHL and at least one common VHL tumor should be tested for VHL variants. People with a family history of VHL disease wanting to know their VHL variant status should also be tested. Earlier diagnosis improves patient prognosis through regular screening and treatment for early-onset malignancies. This test is specifically designed for heritable germline variants and is not appropriate for the detection of somatic variants in tumor tissue.


Official Gene Symbol OMIM ID
VHL 608537
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Erythrocytosis, Familial, 2 AR 263400
Von Hippel-Lindau Syndrome AD 193300

Related Test

Hereditary Leiomyomatosis and Renal Cell Cancer or Fumarase Deficiency via the FH Gene


  • Frantzen C, Links TP, Giles RH. 1993. Von Hippel-Lindau Disease. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle,. PubMed ID: 20301636
  • Maher ER, Neumann HP, Richard S. 2011. von Hippel–Lindau disease: a clinical and scientific review. European Journal of Human Genetics 19: 617–623. PubMed ID: 21386872
  • Maher et al. (1990). "Statistical analysis of the two stage mutation model in von Hippel-Lindau disease, and in sporadic cerebellar haemangioblastoma and renal cell carcinoma." J Med Genet  27: 311–314. PubMed ID: 2352258
  • Nordstrom-O'Brien. (2010). "Genetic analysis of von Hippel-Lindau disease." Hum Mutat 31:521–37. PubMed ID: 20151405
  • Sgambati et al. (2000). "Mosaicism in von Hippel-Lindau disease: lessons from kindreds with germline mutations identified in offspring with mosaic parents." J Hum Genet 66:84–91. PubMed ID: 10631138


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

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2) Select Additional Test Options

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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