Genetic Methylation Testing — the methylation cycle involves dozens of genes beyond MTHFR, and whole genome sequencing evaluates all of them — MTRR, MTR, BHMT, CBS, COMT, MAT1A, AHCY — providing the complete methylation genetic profile.
Whole genome sequencing evaluates all methylation cycle genes simultaneously — not just the two common MTHFR variants (C677T, A1298C) tested by standard panels, but every variant across every gene in the folate, methionine, and transsulfuration pathways.
Genetic Methylation Testing
The methylation cycle (one-carbon metabolism) is a central metabolic pathway that provides methyl groups for DNA methylation, neurotransmitter synthesis, detoxification, phospholipid production, and homocysteine metabolism. The pathway involves multiple enzymes: MTHFR (methylenetetrahydrofolate reductase — converts 5,10-methyleneTHF to 5-methylTHF, the active folate form), MTR (methionine synthase — converts homocysteine to methionine using B12), MTRR (methionine synthase reductase — regenerates active B12 for MTR), BHMT (betaine-homocysteine methyltransferase — alternative homocysteine conversion pathway), CBS (cystathionine beta-synthase — transsulfuration pathway), and COMT (catechol-O-methyltransferase — neurotransmitter methylation).
MTHFR C677T (rs1801133) is the most studied methylation variant: homozygous TT genotype (~10-12% of European ancestry) reduces MTHFR enzyme activity by ~70%, potentially causing elevated homocysteine (a cardiovascular risk factor) and reduced methylfolate availability. MTHFR A1298C (rs1801131) reduces activity by ~35% in homozygotes. However, the methylation cycle is a network — individual variants in other genes (MTRR A66G, MTR A2756G, CBS C699T, COMT Val158Met) can compound or compensate for MTHFR variants. Standard MTHFR-only tests miss this network complexity.
Clinical implications of methylation variants include: elevated homocysteine (cardiovascular risk — addressable with methylfolate and active B12 supplementation), neural tube defect risk in pregnancy (MTHFR TT women benefit from methylfolate rather than folic acid), variable drug metabolism (COMT Val158Met affects catecholamine metabolism, pain sensitivity, and response to certain medications), and CBS variants that may affect sulfur metabolism and detoxification pathways. Comprehensive methylation testing that evaluates the entire pathway — not just one or two MTHFR variants — provides a complete picture for personalized supplementation.
Standard MTHFR tests check only 2 variants (C677T and A1298C). The methylation cycle involves 20+ genes with hundreds of functional variants. WGS evaluates all of them — providing the comprehensive profile that incomplete testing cannot.
Methylation is a pathway, not a single gene. Testing only MTHFR C677T and A1298C misses the majority of genetic variation that affects folate, B12, and homocysteine metabolism. WGS evaluates the complete pathway.
MTHFR-only testing misses the network — MTRR, MTR, BHMT, and CBS variants can compound or compensate for MTHFR genotype
A patient with MTHFR 677 CT (heterozygous, mild reduction) who also carries MTRR 66 GG (reduced B12 recycling) and MTR 2756 GG (reduced methionine synthase activity) may have significantly impaired methylation — more than would be predicted from the MTHFR result alone. Conversely, a patient with MTHFR 677 TT but favorable BHMT and CBS genotypes may compensate through alternative pathways. Only comprehensive testing of the entire pathway reveals the net methylation capacity.
COMT Val158Met affects pain sensitivity, catecholamine metabolism, and response to HRT — a pharmacogenomic variant with broad clinical implications
COMT Val158Met (rs4680) determines COMT enzyme activity: Val/Val (high activity, rapid catecholamine degradation — 'warrior' phenotype), Met/Met (low activity, higher catecholamine levels — 'worrier' phenotype), and Val/Met (intermediate). This variant affects pain sensitivity, stress response, cognitive performance under pressure, estrogen metabolism, and response to certain medications. COMT is part of the methylation cycle — it uses SAM (S-adenosylmethionine) as its methyl donor. WGS provides COMT genotyping alongside all other methylation genes.
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 Genetic Methylation Testing 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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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
