Test Code VHLZZ Von Hippel Lindau Syndrome, VHL, Full Gene Analysis, Varies

Ordering Guidance

For patients suspected of having hereditary erythrocytosis or polycythemia, order HEMP / Hereditary Erythrocytosis Mutations, Whole Blood.

For a comprehensive hereditary cancer panel that includes the VHL gene, consider one of the following tests:

-ENDCP / Hereditary Endocrine Cancer Panel, Varies

-HPGLP / Hereditary Paraganglioma/Pheochromocytoma Panel, Varies

-RENCP / Hereditary Renal Cancer Panel, Varies

Testing for VHL gene as part of a customized panel is available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

Targeted testing for familial variants (also called site-specific or known mutations testing) is available for this gene. For more information see FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

2. Molecular Genetics: Inherited Cancer Syndromes Patient Information Sheet (T519)

3. If not ordering electronically, complete, print, and send a Oncology Test Request (T729) with the specimen.

Secondary ID

614589

Useful For

Evaluating patients with a personal or family history suggestive of Von Hippel-Lindau (VHL) syndrome

Establishing a diagnosis of a VHL allowing for targeted cancer surveillance based on associated risks

Identifying genetic variants associated with increased risk for VHL syndrome allowing for predictive testing of at-risk family members

Special Instructions

Method Name

Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing

Reporting Name

VHL Full Gene Analysis

Specimen Type

Varies

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type	Temperature	Time	Special Container
Varies	Varies

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Clinical Information

Germline variants in the VHL gene are associated with Von Hippel-Lindau (VHL) syndrome, a rare autosomal dominant hereditary cancer syndrome.(1,2) VHL syndrome is characterized by an increased risk of developing a variety of cancerous and non-cancerous tumors and lesions, including hemangioblastomas of the brain or spinal cord, retinal angiomas, renal, pancreatic and epididymal cysts, pheochromocytomas, pancreatic neuroendocrine tumors, endolymphatic cell tumors, and clear cell renal cell carcinoma.(3) While considered a highly penetrant condition, approximately 20% of VHL syndrome cases are due to new (de novo) disease-causing variants, which, in some cases, result in disease mosaicism.(4)

Research has suggested certain combinations of VHL tumors cluster in VHL families, and this may be driven by the type of VHL gene variant present in the family.(4) This observation has led to a phenotype-based classification of VHL syndrome. However, these patterns are not entirely specific and should not necessarily be used for diagnostic or therapeutic purposes.

The National Comprehensive Cancer Network provides recommendations regarding the medical management of individuals with VHL syndrome.

Of note, germline variants in the VHL gene are also associated with autosomal recessive hereditary erythrocytosis or polycythemia. Cases of VHL cancer syndrome and erythrocytosis are largely mutually exclusive, although there is some overlap. For information regarding genetic testing for patients suspected to have hereditary erythrocytosis or polycythemia, see HEMP / Hereditary Erythrocytosis Mutations, Whole Blood.

Reference Values

An interpretive report will be provided.

Interpretation

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(5) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Method Description

Next-generation sequencing (NGS) and/or Sanger sequencing are performed to test for the presence of variants in coding regions and intron/exon boundaries of the VHL gene, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletion-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction-based quantitative method is performed to test for the presence of deletions and duplications in the VHL gene.

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences.(Unpublished Mayo method)

The reference transcript for VHL gene is NM_000551.3. Reference transcript numbers may be updated due to transcript re-versioning. Always refer to the final patient report for gene transcript information referenced at the time of testing.

Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.

Day(s) Performed