MTHFR Mutation
Testing.com is fully supported by readers. We may earn a commission through products purchased using links on this page. You can read more about how we make money here.
- Also Known As:
- MTHFR DNA Testing
- Formal Name:
- Methylenetetrahydrofolate Reductase Mutations
- C677T and A1298C

This page was fact checked by our expert Medical Review Board for accuracy and objectivity. Read more about our editorial policy and review process.
-
1
Order Your Test
Online or over the phone
-
2
Find a Lab Near You
Over 3,500 locations to choose from
-
3
Get Your Results
Sent Directly to You
At a Glance
Why Get Tested?
To evaluate the cause of elevated homocysteine levels; sometimes to help determine your risk of thrombosis or premature cardiovascular disease (CVD), though some expert guidelines do not recommend it
When To Get Tested?
When you have elevated homocysteine levels; sometimes when a close relative has MTHFR gene mutations or has developed CVD or thrombosis at an early age
Sample Required?
A blood sample drawn from a vein
Test Preparation Needed?
None
What is being tested?
The methylenetetrahydrofolate reductase (MTHFR) gene contains the DNA code to produce the MTHFR enzyme. This test detects two of the most common mutations.
When there are mutations or variations in the MTHFR gene, it can lead to serious genetic disorders such as homocystinuria, anencephaly, spina bifida, and others. The MTHFR enzyme is critical for metabolizing one form of B vitamin, folate, into another. It is also part of the process that converts homocysteine into methionine, an important building block for many proteins.
If someone has increased levels of homocysteine, that means the body is not processing it properly. One cause of that could be a mutation in the MTHFR gene, causing homocystinuria. While at least seven unique MTHFR mutations have been found in people with homocystnuria, there are two relatively common DNA sequence variants, known as single nucleotide polymorphisms (SNPs), that are tested. The two MTHFR variants are called C677T and A1298C, and individuals can inherit one or both variants. These SNPs result in changes in the DNA (or mutations) that are associated with decreased MTHFR activity and increased homocysteine levels in the blood, which may increase the risk of premature cardiovascular disease (CVD), formation of inappropriate blood clots (thrombosis), and stroke.
Approximately 5-14% of the U.S. population is homozygous for C677T, meaning that they have two copies of it. There is some ethnic variability in the frequency, with the highest being in those of Mediterranean ancestry and the lowest in those of African ancestry.
The C677T variant results in a less active form of the MTHFR enzyme and reduced ability to process folate and homocysteine. When a person has two copies of the MTHFR C677T gene mutation (homozygous) or one copy of MTHFR C677T and one copy of A1298C (compound heterozygous), decreased MTHFR enzyme activity slows down the homocysteine-to-methionine conversion process and can lead to a buildup of homocysteine in the blood.
The increase in homocysteine is often mild to moderate but will vary from person to person depending upon the amount of MTHFR enzyme activity. Even if a person has two copies of the MTHFR mutation, that person may not develop high homocysteine levels since adequate folate intake can “cancel out” the effect of the MTHFR mutation.
Results of some studies suggest that high levels of homocysteine in the blood may contribute to risk of CVD by damaging blood vessel walls and promoting formation of plaque (atherosclerosis) and inappropriate blood clots. However, a direct link between homocysteine levels and cardiovascular disease or thrombotic risk has not been found. For more on this, see the article on Homocysteine.
Common Questions
View Sources
Sources Used in Current Review
5,10-Methylenetetrahydrofolate Reductase C677T and A1298C Mutations, Blood. Mayo Medical Laboratories. Available online at https://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/61367. Accessed on 8/21/18.
(September 27, 2018) A Genetic Test You Don’t Need. Cleveland Clinic. Available online at https://health.clevelandclinic.org/a-genetic-test-you-dont-need. Accessed on 8/21/18.
Homocysteine. University of Rochester Medical Center. Available online at https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=167&ContentID=homocysteine. Accessed on 8/21/18.
(December 4, 2014) Association Between MTHFR Polymorphisms and Congenital Heart Disease: A Meta-analysis based on 9,329 cases and 15,076 controls. Scientific Reports. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255188. Accessed on 8/22/18.
(February 21, 2012) Homocysteine and Coronary Heart Disease: Meta-analysis of MTHFR Case-Control Studies, Avoiding Publication Bias. PLOS Medicine. Available online at https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001177. Accessed on 8/22/18.
MTHFR Gene Variant. Genetic and Rare Diseases Information Center, National Center for Advancing Translational Sciences, National Institutes of Health. Available online at https://rarediseases.info.nih.gov/diseases/10953/mthfr-gene-variant. Accessed on 8/22/18.
Sources Used in Previous Reviews
Mandava, P, et. al. (Updated 2009 May 25). Metabolic Disease and Stroke – Homocystinuria/Homocysteinemia. eMedicine [On-line information]. Available online at http://emedicine.medscape.com/article/1162007-overview. Accessed October 2010.
(Reviewed 2008 January). MTHFR. Genetics Home Reference [On-line information]. Available online at http://ghr.nlm.nih.gov/gene/MTHFR. Accessed October 2010.
Fong, C. (Revised 2010 February). Amino Acid and Organic Acid Metabolism Disorders. Merck Manual for Healthcare Professionals [On-line information]. Available online at http://www.merck.com/mmpe/sec19/ch296/ch296c.html?qt=MTHFR&alt=sh. Accessed October 2010.
Hart, K. et. al. (Updated 2010 August). Hypercoagulable States – Thrombophilia. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/Thrombophilia.html?client_ID=LTD. Accessed October 2010.
(© 1995-2010). MayoClinic Mayo Medical Laboratories. Unit Code 91457: Methylenetetrahydrofolate Reductase (MTHFR) 2 Mutations [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/91457. Accessed October 2010.
(© 2006-2010). Methylenetetrahydrofolate Reductase (MTHFR) 2 Mutations: 0055655. ARUP’s Laboratory Test Directory [On-line information]. Available online at http://www.aruplab.com/guides/ug/tests/0055655.jsp. Accessed October 2010.
Varga, E. et. al. (2005 May 17). Homocysteine and MTHFR Mutations, Relation to Thrombosis and Coronary Artery Disease. Circulation. 2005;111:e289-e293 [On-line information]. Available online at http://circ.ahajournals.org/cgi/content/full/111/19/e289. Accessed October 2010.
Curtin, K. et. al. (2004 February). MTHFR C677T and A1298C Polymorphisms. Cancer Epidemiology, Biomarkers & Prevention. February 1, 2004 13; 285 [On-line information]. Available online at http://cebp.aacrjournals.org/content/13/2/285.full. Accessed October 2010.
(2005 June 17). MTHFR Gene Variants and Birth Defects. CDC Birth Defects [On-line information] Available online at http://www.cdc.gov/ncbddd/bd/mthfr.htm. Accessed October 2010.
(© 2010). MTHFR DNA Test. Kimball genetics [On-line information]. Available online at http://www.kimballgenetics.com/tests-mthfr.html. Accessed October 2010.
(Reviewed 2011 July). MTHFR. Genetics Home Reference. Available online at http://ghr.nlm.nih.gov/gene/MTHFR. Accessed February 2014.
(© 1995-2014). 5,10-Methylenetetrahydrofolate Reductase C677T, Mutation, Blood. Mayo Medical Laboratories. Available online at http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/81648. Accessed February 2014.
(© 2014). Methylenetetrahydrofolate Reductase (MTHFR) 2 Mutations 0055655. ARUP Laboratories Laboratory Test Directory. Available online at http://ltd.aruplab.com/Tests/Pub/0055655. Accessed February 2014.
Wang W. et al. (2013 March 11). MTHFR C677T Polymorphism and Risk of Congenital Heart Defects: Evidence from 29 Case-Control and TDT Studies. PLOS One. DOI: 10.1371/journal.pone.0058041. Available online at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0058041. Accessed February 2014.
Hickey, S. et al. (3 January 2013). ACMG Practice Guideline: lack of evidence forMTHFR polymorphism testing. Genetics in Medicine. doi:10.1038/gim.2012. Available online at http://www.nature.com/gim/journal/v15/n2/full/gim2012165a.html. Accessed February 2014.
Cohen D.A., et al. (29 November 2013). Laboratory informatics based evaluation of methylene tetrahydrofolate reductase C677T genetic test overutilization. Journal of Pathology Informatics. doi: 10.4103/2153-3539.122389. Available online at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869957/. Accessed February 2014.
Mandava, P. et al. (Updated 2013 June 20). Homocystinuria/Homocysteinemia. Medscape. Available online at http://emedicine.medscape.com/article/1952251-overview#a30. Accessed February 2014.
Ask a Laboratory Scientist
