Tumors starting in organs that shouldn't be making them — kidneys, spine, eyes. One gene, inherited since birth, determining your lifetime.
Whole genome sequencing identifies VHL variants and enables the surveillance protocols that catch tumors early — when treatment options are broadest.
Von Hippel-Lindau Disease
Von Hippel-Lindau (VHL) syndrome is caused by germline pathogenic variants in VHL, a gene encoding a protein component of an E3 ubiquitin ligase complex. Under normal oxygen, pVHL targets hypoxia-inducible factor (HIF) for degradation. When pVHL is dysfunctional, HIF accumulates constitutively, activating genes involved in angiogenesis, cell proliferation, and glucose metabolism — even in the presence of adequate oxygen. This pseudo-hypoxic state drives tumor formation specifically in highly vascularized organs. VHL follows Knudson's two-hit tumor suppressor model: the inherited germline variant inactivates one allele; somatic loss of the remaining allele initiates tumorigenesis.
Von Hippel-Lindau syndrome affects approximately 1 in 30,000–50,000 individuals, with penetrance exceeding 90% by age 65. The syndrome is characterized by multiple tumor types: hemangioblastomas of the brain, spinal cord, and retina (present in 60–80% of carriers), renal cysts and clear cell renal cell carcinoma (occurring in ~70%, the leading cause of mortality), pheochromocytoma/paraganglioma (10–20%), pancreatic neuroendocrine tumors and cysts, endolymphatic sac tumors, and epididymal/broad ligament cystadenomas. Approximately 10% of cases are de novo variants. Average age of VHL diagnosis is 26 years, with range from infancy to the seventh decade.
Identifying a VHL pathogenic variant dramatically changes clinical management. It triggers comprehensive lifelong surveillance beginning in childhood: annual retinal examination from age 1, annual blood pressure monitoring from age 5, annual abdominal MRI from age 15, and biennial brain/spine MRI. This surveillance approach catches renal cell carcinomas and pheochromocytomas at early stages when kidney-sparing surgery is possible, preserving renal function through multiple interventions over a lifetime. Belzutifan, an FDA-approved HIF-2α inhibitor, offers targeted therapy for VHL-associated renal cell carcinoma. Cascade testing identifies relatives at risk before tumors develop.
VHL genotype-phenotype correlations are clinically important: Type 1 variants (no pheochromocytoma risk) have different surveillance protocols than Type 2A/2B/2C variants (pheochromocytoma risk, requiring additional screening).
The VHL gene is small, but approximately 20% of pathogenic variants are large deletions — requiring specialized analysis standard sequencing does not provide.
VHL deletions require deletion-duplication analysis standard panels lack
VHL is a relatively small gene (3 exons), which typically allows high detection rates with standard sequencing. However, approximately 20% of VHL pathogenic variants are partial or complete gene deletions. Standard short-read sequencing excels at detecting point mutations and small insertions/deletions but struggles with large structural rearrangements. Many commercial panels do not include deletion/duplication analysis for VHL — requiring separate, often cumbersome testing. Mosaic VHL variants at low allelic fractions may be missed by standard sequencing depth. Whole genome sequencing detects both point mutations and structural variants in a single analysis.
A VHL finding opens a surveillance protocol that saves lives
Confirmation of VHL triggers the most comprehensive single-gene surveillance protocol in medical genetics. Annual retinal exams from age 1 catch optic pathway complications early. Annual abdominal MRI from age 15 detects kidney cancers and pheochromocytomas at early stages — when kidney-sparing surgery preserves renal function across multiple operations spanning a lifetime. Belzutifan (Welireg), an FDA-approved HIF-2α inhibitor, offers targeted therapy specifically for VHL-associated renal cell carcinoma, representing a genotype-matched treatment option.
Your full DNA (not just a part of it)
Traditional genetic testing looks at narrow sets of genes, missing most parts of your genome. We sequence your full genome — every gene and every region between genes.
Comprehensive insights and specialized reports
Easy to read and with answers you and your doctor can act on. Not a file to interpret — 200+ clinical reports, organized by category.
Your test becomes more valuable every year
Your DNA does not change, but genome science is accelerating. Every month, new variant-disease associations are discovered. We validate these findings and update your reports automatically. Your test becomes more valuable every year.
The results doctors bring to their hardest cases.
Forty years of uncertainty. One test.
A patient had spent decades in the UK healthcare system without a diagnosis. Dante data, accepted by NHS clinical teams at Queen Elizabeth University Hospital Glasgow, identified Noonan Syndrome and a RUNX1 leukemia-associated variant that had gone undetected. After 40 years, they finally had an answer.
A complete read delivers a complete picture.
A patient came to Dante to investigate periodic paralysis. Reading the complete genome identified a concurrent hereditary cardiac finding — Brugada syndrome — that their doctor confirmed with an ECG. The result also explained a family member's unresolved cardiac history. One test. Every answer in it.
Sequenced in 2019. The data worked in 2021.
Jennifer sequenced her genome with Dante two years before her breast cancer diagnosis. When treatment began, Dante's pharmacogenomics data showed her prescribed chemotherapy would cause serious adverse effects. Her doctor selected an alternative — and she started effective treatment from day one.
Every genetic question deserves a complete answer.
Whether you are searching for answers today or protecting your health for tomorrow, a complete read of your entire genome is the only place to start.
It runs in your family. Now you can know if it runs in your genes.
Your genome contains inherited variants associated with medical conditions like cardiac, cancer, and neurological. We read all of them — with the clinical depth to give the result meaning.
Learn more →When traditional lab tests say you're fine. And you know you're not.
Standard diagnostic tests check for a pre-selected set of answers. We sequence your full DNA — including parts that no test was designed to check. If the answer is in your genome, we will help you find it.
Learn more →Your diagnosis may be right. Your treatment plan may be incomplete.
Your genes determine which treatments are most likely to work — and which are not. We give your doctor the tools and insights to inform your treatment plan.
Learn more →You want to know before something forces the question.
Some people don't wait for a diagnosis or a family history to act. Whole genome sequencing gives you the complete genetic picture now — so you and your doctor can make informed decisions before anything becomes urgent.
Learn more →You already took a DNA test. Here's what it couldn't tell you.
Most consumer DNA tests read less than 0.1% of your genome. We read all of it.
Learn more →Clinical-grade results. Chosen by individuals, trusted by doctors for their most complex cases.
Dante Genome Test helped specialists at a UK national acute hospital in the identification of Noonan Syndrome and a rare leukemia-associated genetic variant that had gone undetected. That result changed the medical care of the patient.
Accredited by & published in
Common questions about whole genome sequencing.
What is the difference between whole genome sequencing and a targeted genetic test?
Targeted genetic tests — including standard hereditary cancer panels — read a pre-defined list of known variants in a specific set of genes. They are designed to find what they already know to look for. Whole genome sequencing reads your entire genome: all 6 billion base pairs, every gene, every region between genes. A Mayo Clinic study published in JAMA Oncology found that standard testing guidelines missed more than half of patients with inherited cancer mutations. Genome Test does not have a fixed list.
What will I receive when my results are ready?
Your Dante Genome delivers 200+ physician-ready reports organized by clinical category — hereditary cancer, cardiac conditions, rare diseases, pharmacogenomics, carrier status, and more. Reports are delivered to your secure Genome Manager and are formatted for direct clinical use. Your genome data is permanently retained and re-analyzed automatically as science advances.
What happens if a clinically significant variant is found?
If a pathogenic or likely-pathogenic variant is identified, it will be clearly flagged in your physician-ready report with clinical context, published evidence, and recommended next steps. We recommend sharing any clinically significant finding with your physician or a genetic counselor, who can guide decisions about surveillance, risk reduction, or cascade testing for family members.
How is this different from a consumer DNA test like 23andMe or AncestryDNA?
Consumer DNA tests use genotyping chips that read less than 0.1% of your genome — a tiny pre-selected set of common variants. They are optimized for ancestry and population-level traits, not clinical genetic findings. The Dante Genome Test sequences 100% of your genome at 30X coverage, the same standard used in clinical diagnostic settings. The two tests are not comparable in scope, methodology, or clinical utility.
How long does it take to get results, and how are they delivered?
Your collection kit ships within 48 hours of ordering. Once your sample arrives at our CLIA-certified laboratory, sequencing and analysis takes 6–8 weeks. Results are delivered securely to your Genome Manager, where you can access your reports, share them with your physician, and receive automatic updates as new findings are validated against your genome.
We work with patient advocacy groups worldwide.
Dante Labs works with patient advocacy groups of any size — for Von Hippel-Lindau Disease and other conditions, rare and common. We support groups in any country, including virtual patient advocacy groups.
We can provide customized reports, group discounts, and packages tailored for your members. Please reach out using the form and we'll be in touch within two business days.
- Custom genomic reports for your members
- Group discounts and tailored packages
- Any country — including virtual groups
- Rare and common conditions covered
Message received.
We’ll be in touch within 2 business days. To follow up directly: hello@dantelabs.com
One test.
A lifetime of answers.
One kit, sent to your home. Your entire genome sequenced at the clinical standard used for diagnostic decisions. 200+ physician-ready reports delivered to your Genome Manager in 6–8 weeks — permanent and updated as science advances.
Ships within 48 hours · Results in 6–8 weeks
