Heart palpitations during exercise. A family member with an unexplained cardiac event. The connection between the two could be a single gene — and knowing changes everything.
Whole genome sequencing identifies desmosomal mutations driving arrhythmogenic cardiomyopathy, revealing risk in family members and enabling proactive cardiac screening and management.
Arrhythmogenic Cardiomyopathy (ARVC)
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty replacement of myocardium, predominantly affecting the right ventricle, which predisposes to ventricular arrhythmias, heart failure, and sudden cardiac death — particularly during exercise. Prevalence is estimated at 1 in 1,000 to 1 in 5,000. ARVC is a leading cause of sudden cardiac death in young athletes and accounts for up to 20% of sudden death cases in those under 35 years old. Inheritance is autosomal dominant with incomplete penetrance and variable expressivity. Approximately half of ARVC cases are familial; the other half result from de novo variants. Left-dominant and biventricular variants of ARVC are now recognized, expanding the original right-ventricular-dominant phenotype.
Three desmosomal genes account for the majority of ARVC cases. PKP2 (plakophilin-2) is the most frequently mutated gene, found in 20–46% of ARVC cases and predominantly associated with classic right-dominant disease. DSP (desmoplakin) and DSG2 (desmoglein-2) each account for approximately 10% of cases and are more frequently associated with biventricular or left-dominant phenotypes with higher heart failure risk. These proteins form the cardiac desmosome, the mechanical junction that couples cardiomyocytes. Pathogenic variants weaken cell-cell adhesion, particularly under mechanical stress (exercise), triggering cardiomyocyte detachment and replacement by fibrofatty scar tissue.
Identifying an ARVC mutation has major implications for patient management and family screening. Affected individuals are advised to restrict strenuous exercise, which is a potent trigger for arrhythmias. Medical therapy with beta-blockers and antiarrhythmic drugs (sotalol, amiodarone) is initiated. Implantable cardioverter-defibrillators (ICDs) are recommended for patients with recurrent arrhythmias or family history of sudden death. Genetic testing enables cascade screening of relatives — identifying asymptomatic mutation carriers who may have no cardiac symptoms yet but who benefit from surveillance and activity restriction. Gene-specific risk stratification is now recognized: PKP2 variants generally have better prognosis than DSP or DSG2 variants.
PKP2, DSP, and DSG2 variants differ in their phenotypic expression — PKP2 typically right-dominant, DSP and DSG2 more often biventricular or left-dominant with higher heart failure risk.
Standard ARVC panels test 5–8 desmosomal genes but find mutations in only 40–60% of clinically diagnosed patients.
The mutation may be in a region standard panels miss
Standard ARVC panels typically test 5–8 desmosomal genes plus select non-desmosomal genes. However, a pathogenic variant is identified in only 40–60% of patients meeting clinical diagnostic criteria for ARVC. The remaining cases may involve non-desmosomal genes, digenic or oligogenic inheritance, deep intronic variants affecting splicing, or complex structural variants not detected by standard sequencing. PKP2 is particularly challenging — missense variants are common but difficult to interpret due to high background variation. VUS rates are high in desmosomal genes. Whole genome sequencing captures the full sequence including non-coding regions and enables detection of structural variants.
A finding enables activity restriction and preventive ICD placement
When a pathogenic desmosomal mutation is confirmed, it triggers cascade testing of first-degree relatives — identifying asymptomatic mutation carriers who may have no ECG abnormalities yet. Management becomes gene-informed: PKP2 carriers typically have better long-term prognosis and may tolerate some athletic activity; DSP and DSG2 carriers warrant more stringent activity restriction and lower threshold for ICD implantation. Medical therapy with beta-blockers and antiarrhythmics is initiated. For high-risk carriers with prior arrhythmias or family history of sudden death, ICD placement is a life-saving intervention. Early identification of at-risk relatives through cascade genetic testing enables preventive strategies before the first arrhythmia occurs.
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.
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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 Arrhythmogenic Cardiomyopathy (ARVC) 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
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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
