TTR Cardiac Amyloidosis — a treatable cause of heart failure hiding in plain sight, where tafamidis reduces mortality by 30% but requires TTR genotyping that most cardiologists have not yet ordered.
Whole genome sequencing identifies all TTR variants — including Val122Ile (carried by 3-4% of African Americans) and Val30Met (the most common hereditary ATTR variant) — providing the molecular diagnosis that unlocks tafamidis therapy.
Hereditary Amyloidosis — ATTR Wild-Type & Variant
Transthyretin amyloid cardiomyopathy (ATTR-CM) is caused by misfolding and deposition of transthyretin (TTR) protein as amyloid fibrils in the myocardium, producing restrictive cardiomyopathy with heart failure. Two forms exist: hereditary ATTR (hATTR, caused by >130 known TTR pathogenic variants) and wild-type ATTR (wtATTR, previously called 'senile cardiac amyloidosis,' caused by age-related misfolding of normal TTR protein). Combined prevalence is dramatically higher than previously recognized — studies suggest ATTR-CM is present in 6-13% of patients with heart failure with preserved ejection fraction (HFpEF) and 5-16% of patients undergoing transcatheter aortic valve replacement.
The TTR Val122Ile variant (p.Val142Ile using current nomenclature) is carried by approximately 3-4% of African Americans — among the most common pathogenic variants of any gene in any population. Val122Ile causes late-onset cardiac amyloidosis, typically presenting after age 60 with progressive heart failure, conduction abnormalities, and carpal tunnel syndrome. It is frequently misdiagnosed as hypertensive heart disease or idiopathic HFpEF in African American patients. The Val30Met variant (p.Val50Met) is the most common hereditary ATTR variant globally, prevalent in Portugal, Sweden, and Japan, and causes both polyneuropathy and cardiomyopathy.
Tafamidis (Vyndamax/Vyndaqel), a TTR stabilizer that prevents tetramer dissociation and amyloid fibril formation, was FDA-approved in 2019 for ATTR cardiomyopathy. The ATTR-ACT trial demonstrated that tafamidis reduced all-cause mortality by 30% and cardiovascular hospitalization by 32% compared to placebo — one of the largest mortality benefits of any heart failure therapy. However, tafamidis requires confirmed ATTR-CM diagnosis, and molecular TTR genotyping is essential to distinguish hereditary from wild-type ATTR (both are treated with tafamidis, but hereditary ATTR has implications for family screening). Gene-silencing therapies (patisiran, inotersen, vutrisiran) are approved for hATTR polyneuropathy.
3-4% of African Americans carry TTR Val122Ile — making it one of the most common pathogenic variants in any population. Late-onset heart failure in African Americans should prompt TTR genotyping.
ATTR-CM is treatable with tafamidis (30% mortality reduction) but is missed in the majority of affected patients. Adding TTR genotyping to heart failure evaluation identifies a treatable subset currently dying of 'idiopathic' heart failure.
30% mortality reduction with tafamidis — but only patients with confirmed ATTR-CM diagnosis receive it
The ATTR-ACT trial demonstrated that tafamidis produces a 30% reduction in all-cause mortality in ATTR cardiomyopathy — among the largest mortality benefits in heart failure therapeutics. Yet autopsy studies suggest that ATTR-CM is present in 20-25% of elderly patients with heart failure who were never diagnosed during life. The gap between treatable disease and actual treatment is enormous. TTR genotyping identifies the hereditary component, and nuclear scintigraphy (99mTc-PYP/DPD scan) diagnoses ATTR-CM non-invasively without biopsy. WGS identifies TTR variants as part of a comprehensive genomic evaluation, flagging ATTR-CM risk before clinical heart failure develops.
Hereditary ATTR requires family cascade screening — all first-degree relatives should be genotyped and monitored
When a TTR pathogenic variant is identified, all first-degree relatives have a 50% chance of carrying the same variant. Presymptomatic carriers benefit from regular cardiac surveillance (echocardiography, cardiac biomarkers, nuclear scintigraphy) to detect subclinical amyloid deposition before heart failure develops — enabling early tafamidis initiation when treatment is most effective. Without molecular TTR diagnosis, the proband is diagnosed with 'cardiac amyloidosis' but family members are not screened, missing the opportunity for presymptomatic intervention.
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.
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Easy to read and with answers you and your doctor can act on. Not a file to interpret — 200+ clinical reports, organized by category.
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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.
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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.
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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.
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Dante Labs works with patient advocacy groups of any size — for Hereditary Amyloidosis — ATTR Wild-Type & Variant 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.
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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
