As genetic testing gets easier, a lot of companies are offering direct-to-consumer (DTC) testing. One test that gets a lot of attention is for the MTHFR polymorphisms C677T and A1289C. In the past, this testing was done only in certain scenarios, such as when individuals had blood clots or recurrent pregnancy losses. However, as scientists have learned more about these common genetic variants, the recommendations about testing for them have changed.
Why is MTHFR gaining popularity?
Most of our genes, including MTHFR, come in two copies: one from our mother and one from our father. The MTHFR gene is like a long sentence, and two variants, C677T and A1289C, are misspellings of the gene that slightly reduce the enzyme’s functionality. We have known about these variants for many years, but we are just now learning how common they are and what they having these variants means for patients. Population screening has shown that over 30% of the population has one of these variants, and most people do not have any symptoms.
What do we know about MTHFR?
These two variants are not responsible for blood clots. Other disease-causing variants in MTHFR cause a rare condition called homocystinuria where individuals are at risk for clots and other health concerns. However, C677T and A1289C do not cause homocystinuria. The American College of Medical Genetics (ACMG) and other societies no longer recommend testing for these variants.1
The MTHFR protein is responsible for converting folate to an active form in the body. There is some evidence that pregnant people with two identical copies (called homozygous) of C677T or A1289C are at increased risk of having a child with a neural tube defect. However, supplementation with folic acid during pregnancy significantly reduces this risk regardless of one’s genetic status. Taking special forms of folate are not necessary, even for those with the MTHFR variants.2
What are the concerns about testing for these variants?
Some companies offer MTHFR screening directly to the consumer. Concerns with this type of testing are:
- No current medical society recommends routine testing for these variants.
- It is important to research a company’s privacy statements to know who is receiving your genetic data, what they will do with it, and what other information they may take from your DNA. These companies often do not operate under the same privacy laws that are required of your medical team.
- Even if you do test positive for these variants, you do not need to take special forms of folate. Your enzyme functions well enough to change folic acid into the active form. Most people get enough folate from a well-balanced diet. Please speak with your doctor if you are concerned that you may not be getting enough folate.
What are we still learning?
We are still learning if having one or two of these variants will interact with the way certain drugs work in the body.3 At present, there is no evidence that population-wide testing for these variants is necessary. A genetic professional or other specialist may recommend testing if it can inform treatment decisions.
References
- Moll S, Varga EA. Homocysteine and MTHFR Mutations. Circulation. 2015;132(1):e6-e9. doi:10.1161/CIRCULATIONAHA.114.013311
- CDC. MTHFR Gene Variant and Folic Acid Fact. February 10th 2026. https://www.cdc.gov/folic-acid/data-research/mthfr/index.html
- Schwahn, BC, Rozen R. Methylenetetrahydrofolate Reductase Polymorphisms: Pharmacogenetic Effects. In: Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-2013. Available from: https://www.ncbi.nlm.nih.gov/books/NBK5968/
As genetic testing gets easier, a lot of companies are offering direct-to-consumer (DTC) testing. One test that gets a lot of attention is for the MTHFR polymorphisms C677T and A1289C. In the past, this testing was done only in certain scenarios, such as when individuals had blood clots or recurrent pregnancy losses. However, as scientists have learned more about these common genetic variants, the recommendations about testing for them have changed.
Why is MTHFR gaining popularity?
Most of our genes, including MTHFR, come in two copies: one from our mother and one from our father. The MTHFR gene is like a long sentence, and two variants, C677T and A1289C, are misspellings of the gene that slightly reduce the enzyme’s functionality. We have known about these variants for many years, but we are just now learning how common they are and what they having these variants means for patients. Population screening has shown that over 30% of the population has one of these variants, and most people do not have any symptoms.
What do we know about MTHFR?
These two variants are not responsible for blood clots. Other disease-causing variants in MTHFR cause a rare condition called homocystinuria where individuals are at risk for clots and other health concerns. However, C677T and A1289C do not cause homocystinuria. The American College of Medical Genetics (ACMG) and other societies no longer recommend testing for these variants.1
The MTHFR protein is responsible for converting folate to an active form in the body. There is some evidence that pregnant people with two identical copies (called homozygous) of C677T or A1289C are at increased risk of having a child with a neural tube defect. However, supplementation with folic acid during pregnancy significantly reduces this risk regardless of one’s genetic status. Taking special forms of folate are not necessary, even for those with the MTHFR variants.2
What are the concerns about testing for these variants?
Some companies offer MTHFR screening directly to the consumer. Concerns with this type of testing are:
- No current medical society recommends routine testing for these variants.
- It is important to research a company’s privacy statements to know who is receiving your genetic data, what they will do with it, and what other information they may take from your DNA. These companies often do not operate under the same privacy laws that are required of your medical team.
- Even if you do test positive for these variants, you do not need to take special forms of folate. Your enzyme functions well enough to change folic acid into the active form. Most people get enough folate from a well-balanced diet. Please speak with your doctor if you are concerned that you may not be getting enough folate.
What are we still learning?
We are still learning if having one or two of these variants will interact with the way certain drugs work in the body.3 At present, there is no evidence that population-wide testing for these variants is necessary. A genetic professional or other specialist may recommend testing if it can inform treatment decisions.
References
- Moll S, Varga EA. Homocysteine and MTHFR Mutations. Circulation. 2015;132(1):e6-e9. doi:10.1161/CIRCULATIONAHA.114.013311
- CDC. MTHFR Gene Variant and Folic Acid Fact. February 10th 2026. https://www.cdc.gov/folic-acid/data-research/mthfr/index.html
- Schwahn, BC, Rozen R. Methylenetetrahydrofolate Reductase Polymorphisms: Pharmacogenetic Effects. In: Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-2013. Available from: https://www.ncbi.nlm.nih.gov/books/NBK5968/
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