Sanger Sequencing of VHL Only for Von Hippel-Lindau Syndrome (VHL1)
Information for Ordering
Acceptable Specimen Types
- Fresh blood sample: 3–6 mL EDTA; no time limitations associated with receipt
- DNA extracted from lymphocyte cells: minimum volume of 25 µL containing 3 µg of DNA; A260/A280 ratio ≥1.8; must be extracted in a CLIA-certified or equivalent laboratory
Turnaround Time
- Blood or DNA: Average of 15 working days
Price, CPT Codes, and Z Code
- Institutional/self-pay price: $650 USD
- CPT codes: 81404 and 81403
- Z code: ZB68F
Candidates for Testing
Patients seeking molecular confirmation of a clinical diagnosis of Von Hippel-Lindau syndrome, including patients presenting with only one characteristic manifestation of the condition.
Specimen Shipping and Handling
Please refer to the specimen requirements listed above.
Blood and extracted DNA specimens should be shipped at room temperature. Do not ship specimens on ice.
Specimens must be packaged to prevent breakage. Absorbent material must be included to contain liquids if breakage occurs. Specimens must also be shipped in double watertight containers, such as a specimen pouch placed inside the shipping company’s diagnostic envelope.
To request a collection kit, please complete the Collection Kit Request Form.
Before shipping a specimen, please contact the UAB Medical Genomics Laboratory by email at medgenomics@uabmc.edu or by phone at 205-934-5562. Please provide the specimen type, shipment date, and package tracking number so the laboratory can help ensure proper and timely receipt.
Required Forms
About
Disorder Background
Von Hippel-Lindau syndrome is an autosomal dominant tumor-predisposition disorder with high penetrance, approaching complete penetrance by 60 years of age. It is characterized by hemangioblastomas of the central nervous system and retina and may involve other visceral organs.
Individuals with Von Hippel-Lindau syndrome also have an increased risk of clear cell renal cell carcinoma, pheochromocytoma, renal cysts, pancreatic cysts, pancreatic cystadenomas, and pancreatic neuroendocrine tumors. The condition affects approximately 1 in 35,000–36,000 individuals and occurs across all populations and sexes.
The official name of the VHL gene is von Hippel-Lindau tumor suppressor. The gene is located on chromosome 3p25.3, contains three exons, and encodes an approximately 4.5 kb messenger RNA.
Loss-of-function variants in VHL are the only established cause of Von Hippel-Lindau syndrome, and germline variants can be identified in nearly all affected families. Pathogenic variants are distributed throughout the coding region.
Missense variants account for approximately 40% of identified germline variants. Small deletions, insertions, splice-site variants, and nonsense variants account for approximately 30%. Large deletions account for approximately one-third of germline variants, including whole-gene deletions. The de novo variant rate is estimated at approximately 20%, and mosaicism may occur in a small percentage of affected individuals.
Test Description
The VHL-only Sanger sequencing test begins with DNA extraction followed by amplification of the three coding exons of VHL. The resulting PCR products are used as templates for direct bidirectional Sanger sequencing.
MLPA copy-number analysis is also performed to detect multi-exon deletions or duplications and whole-gene deletions.
View references for this testing.
For more information, test requisition forms, or collection kits, please contact the UAB Medical Genomics Laboratory at 205-934-5562 or medgenomics@uabmc.edu.