Skip to content
Blood Test Tracker

MTHFR C677T

A gene test for a very common MTHFR variant that slightly lowers how your body handles folate. Medical groups advise against routine testing for clots.

AI-verified against cited sources. Awaiting expert reviewAlso called C677T, 677C>TLOINC 28005-7

What it is

MTHFR is a gene that makes an enzyme your body uses to handle folate (vitamin B9) and homocysteine. The C677T variant is very common and lowers the enzyme's activity a little, mostly in people with two copies. You get one copy of the gene from each parent, so the result is CC (no copies of the variant), CT (one copy) or TT (two copies). Some labs call it a mutation, but it is an ordinary variation. It is a one-time DNA test, and the result never changes.

Why it matters

People are often tested because of worries about blood clots, pregnancy loss or folate. The American College of Medical Genetics and Genomics (ACMG) says MTHFR testing should not be part of a routine work-up for clotting problems, and the American Society of Hematology lists MTHFR variants among changes shown not to be linked to blood clots in the veins. A homocysteine or folate blood test usually tells you more about what is happening in your body now. Most people with CT or TT are healthy.

If it’s high

A CT or TT result means you carry one or two copies of a common variant. One copy (CT) is unlikely to matter for your health. Two copies (TT) can raise homocysteine a little, mostly when folate intake is low, and the effect is usually mild. The American Society of Hematology says this variant has been shown not to be linked to blood clots in the veins, and most people with CT or TT have no health problems. Your clinician may check a homocysteine level if you have TT.

Common causes

  • You inherited the variant from one or both parents. It is very common worldwide.
  • Ancestry: roughly 25% of Hispanic people and 10 to 15% of white people in North America have two copies

What can help

  • Ask your clinician whether a homocysteine blood test would tell you more than the gene result
  • Get folate from food, such as dark green leafy vegetables, beans and peas, citrus fruit, and fortified breads and cereals
  • If you could become pregnant, ask your clinician about folic acid, which is advised before and during pregnancy whether or not you have this variant
  • Tell your care team about your result if you are ever offered a medicine that works through folate, such as methotrexate

What can affect your result

  • Ancestry: two copies (TT) are more common in some groups than others
  • Folate intake and fortified foods change blood folate and homocysteine more than this gene does
  • Some lab reports print both MTHFR variants (C677T and A1298C) on one line. They are separate results.
  • The test reads your DNA, so fasting, medicines, pregnancy and illness do not change it
  • Diet, fasting, folate supplements and medicines do not change this result, because the test reads inherited DNA. Blood folate and homocysteine levels do respond to diet and supplements, but the gene result does not.
  • Some reports print both MTHFR variants (C677T and A1298C) on one line, and LOINC has a combined code for that (94414-0). They are two separate results.
  • A previous bone marrow (stem cell) transplant from a donor could affect any DNA test on blood, because the DNA may come from the donor's cells.

The result does not change over time, because it reflects DNA you inherited.

When to talk to a clinician

A CT or TT result is not an emergency and does not mean you will have a clot. Whatever your result, call 911 or your local emergency number for chest pain, trouble breathing, coughing up blood or fainting, and contact a clinician promptly if one leg or arm becomes red, warm, swollen or painful.

Questions you could ask

  • Why was this test ordered for me, and what decision would it help with?
  • Does this result change anything about my care, or is it just background information?
  • Would a homocysteine or folate blood test tell us more than this gene result?
  • If I could become pregnant, what should I know about folate and this result?

Questions people ask

Do I need to avoid folic acid or take a special form of folate because of MTHFR?

The CDC says people with an MTHFR variant can process all types of folate, including folic acid, and that how much folic acid you get matters more for your blood folate than your genotype does. If you are thinking about supplements, especially if you could become pregnant, ask your clinician what is right for you.

Does the MTHFR variant cause blood clots or miscarriage?

The American Society of Hematology says the common MTHFR variants have been shown not to be linked to blood clots in the veins. The ACMG says people with two copies and a normal homocysteine level can be reassured that there is no evidence of added clot or repeat pregnancy loss risk from MTHFR. Many other things can cause these problems, so talk with your clinician if you have had one.

Why do some clinics and websites still offer this test?

Years ago, researchers thought a weaker MTHFR enzyme might cause clots and pregnancy loss by raising homocysteine. Later studies did not support that, but the test stayed popular. The ACMG said in 2013 that testing has little clinical use, and reaffirmed that in 2020. It can help to ask your clinician what question this test would answer for you.

Show the science and sources

For clinicians and researchers

MTHFR encodes 5,10-methylenetetrahydrofolate reductase, which converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the main circulating form of folate and a cosubstrate for remethylating homocysteine to methionine. C677T (rs1801133) is c.665C>T, p.Ala222Val in current notation. This missense change makes the enzyme thermolabile with reduced activity, which raises homocysteine mainly when folate status is low. More than 25% of Hispanic people and 10 to 15% of North American white people are homozygous (ACMG 2013; MedlinePlus Genetics). The ACMG 2013 statement found little clinical utility and advised against ordering MTHFR testing as part of a routine thrombophilia evaluation; in April 2020 it was reaffirmed and reclassified as a Clinical Practice Resource because it no longer meets the criteria for an evidence-based guideline. The paper also notes that ACOG does not recommend measuring homocysteine or MTHFR polymorphisms when evaluating venous thromboembolism. ASH 2023 leaves MTHFR c.677C>T and c.1298A>C out of thrombophilia testing because they are not associated with VTE. ACMG describes the heterozygous genotype as unlikely to be clinically significant, suggests a fasting total homocysteine in homozygotes, and says homozygotes with normal homocysteine can be reassured that there is no evidence of increased venous thromboembolism or recurrent pregnancy loss risk related to MTHFR. It also reports a modest increase in neural tube defect risk for offspring of homozygous women (odds ratio 1.6) and a possible weak association with stroke, and notes that older studies outside North America found a modest link with thromboembolism that is no longer seen in North America, possibly because US folic acid fortification lowered homocysteine. CDC states that people with MTHFR variants can process all forms of folate, including folic acid. Targeted genotyping is offered by more than 50 US CLIA laboratories (ACMG 2013). LOINC 28005-7 is the single-variant result; 94414-0 is a combined C677T and A1298C result, which should be split into two markers.

LOINC 28005-7 (primary), 94414-0, 21709-1. Specimen: whole-blood.

Sources

  1. ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing, Genetics in Medicine (2013)
  2. Addendum: ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing, Genetics in Medicine (2020)
  3. American Society of Hematology 2023 guidelines for management of venous thromboembolism: thrombophilia testing, Blood Advances (2023)
  4. MTHFR gene, MedlinePlus Genetics, National Library of Medicine
  5. MTHFR Gene Variant and Folic Acid Facts, Centers for Disease Control and Prevention (2026)
  6. Folic acid in diet, MedlinePlus Medical Encyclopedia, National Library of Medicine
  7. rs1801133 (MTHFR c.665C>T, p.Ala222Val), NCBI dbSNP

AI-verified against cited sources. Awaiting expert review. Last reviewed 2026-10-03. How we build and check these pages.

Related markers