MTHFR Gene Mutations and DNA Tests

Updated August 8, 2019

This article was scientifically reviewed by Jessica Bucher

We take the information we share seriously. Review our Editorial Policy Here.

A list of references is also included at the bottom of this article.

Genetic mutations are responsible for countless anomalies, diseases and disorders. For decades, medical professionals have fine-tuned DNA tests that unlock the genetic code and tell a person how their genes affect their health.

What's in this Guide?

Disclaimer: Before You Read

It is important to know that your genes are not your destiny. There are various environmental and genetic factors working together to shape you. No matter your genetic makeup, maintain ideal blood pressure and glucose levels, avoid harmful alcohol intake, exercise regularly, get regular sleep. And for goodness sake, don't smoke.

Genetics is a quickly changing topic.

One DNA test that has gotten more attention in recent years analyzes the MTHFR gene.

YourDNA can tell you more about this gene and why genetic testing for MTHFR mutations is sometimes discussed.

What Is an MTHFR Variant?

MTHFR variants are connected to the MTHFR gene. The gene helps the body produce methylenetetrahydrofolate reductase (MTHFR), an enzyme that breaks down an amino acid that processes proteins (homocysteine).

It also converts folic acid and folate into L-methylfolate. When an MTHFR variant occurs, it can alter how nutrients are metabolized and converted in the body.

The first step to understanding the MTHFR gene is understanding that different genetic changes, or spelling changes in the gene, have different names.

First of all, everyone has two copies of the MTHFR gene, one from their mother and one from their father.

The sequence of letters within this gene may have variations from the normal genetic code, called variants. Variants are classified by severity.

Some MTHFR variants, called MTHFR mutations or pathogenic variants, cause significant problems with how the gene functions.

MTHFR mutations are rare genetic changes that cause rare disease in the population when individuals have two abnormal copies of the gene, or two mutations.

MTHFR mutations are typically associated with a rare genetic disease called “Homocystinuria” 1. In Homocystinuria, individuals have very low enzyme levels.

If left untreated, individuals with Homocystinuria may develop delays in development, seizures, low muscle tone, and other neurological symptoms. Most states screen newborns for Homocystinuria a few days after birth.

MTHFR variants called “MTHFR polymorphisms” are much more common and may not necessary change how the gene works. If the polymorphisms do affect gene function, it is typically in a mild way.

The common polymorphisms are typically what people have become aware of.

You may have heard that MTHFR polymorphisms may affect both your mental and physical health. Some studies have found associations to the following symptoms, but other studies have shown no real association 2:

  • Depression
  • Bipolar disorder
  • Schizophrenia
  • Attention deficit hyperactivity disorder (ADHD)
  • Autism
  • Cardiovascular disease (CVD)
  • Thrombosis
  • Stroke
  • Early miscarriages and stillbirth
  • Migraines
  • Osteoporosis
  • Colon cancer
  • Acute lymphoblastic leukemia
  • Miscarriage
  • Cleft lip and/or palate

As with any of these common, complex symptoms, many different factors from genetic to environmental, likely contribute to the risk of developing the condition.  Many of these factors are unknown.

Therefore, even if a polymorphism may increase someone’s risk of developing a symptom, it is likely that the polymorphism is not acting alone if symptoms are present. Most of the time, treatment is not different for people with MTHFR polymorphisms 3.

Polymorphisms of the MTHFR Gene

Like all genes, the MTHFR gene can have numerous variants. There can actually be one, two or no variants present in a person. Two common MTHFR polymorphisms that have been heavily studied are:

C677T - When there are two copies of the C677T polymorphism, it’s an MTHFR homozygous C677T polymorphism. This means an individual has two copies of the polymorphism, one from their mother and one from their father.

This homozygous polymorphism occurs in about a quarter of Hispanic Americans and 10-15% of Caucasian Americans 4. Women that have this type of homozygous MTHFR polymorphism may have a higher risk of giving birth to a baby with neural tube defects 5.

The CDC recommends that all women of reproductive age take 400 mcg of Folic acid each day to help prevent neural tube defects 6. If a woman has had a previous child with a neural tube defect, they should discuss increasing this dose with their doctor.

However, having these polymorphisms does not typically mean that an increased dose is necessary.

A1298C - On its own, having one copy of this polymorphism doesn’t increase heart disease risk. Upwards of 20% of Americans have the A1298C variant.

Risks associated with having one A1298C polymorphism on one gene, and one C677T polymorphism on the other gene may be the same or slightly lower than having two C677T polymorphisms 7.

These are the well-known polymorphisms. However, there are also more rare variants in MTHFR. Medical researchers believe there are more than 40 MTHFR variants.

Symptoms of the MTHFR gene changes

What symptoms might someone have if they have a genetic change in the MTHFR gene? The most likely answer is none. There are many healthy people with polymorphisms in this gene.

Alternatively, people with Homocystinuria will likely have severe symptoms. Individuals with Homocystinuria have rare disease-causing genetic variants, called mutations, that severely affect the MTHFR gene.

This typically causes high levels of homocysteine in the blood and urine. As a result, symptoms may include global developmental delay, seizures, blood clots, stroke, and small head size (microcephaly).

Most states screen for this condition on an infant’s newborn screen in the first few days of life.

It is easy to see why information on the MTHFR gene can be so confusing. Even there are many studies looking at the symptoms associated with the MTHFR common polymorphisms, results are conflicting.

One study may say there is an increased risk for certain symptoms, but there is another study saying that there is no increased risk.

Here is what we know when it comes to symptoms of genetic changes in the MTHFR gene:

  • It is hard to determine if symptoms are truly related to the MTHFR gene unless an individual truly has Homocystinuria. Most symptoms that might be associated are caused by a combination of factors including environment, lifestyle, and other genetic changes.
  • To date, there are hundreds of medical conditions that have been researched. Some studies show an association between elevated homocysteine levels and MTHFR common polymorphisms, while others show no association. This is likely because the conditions or symptoms are likely caused by a combination of factors.
  • If an individual does not have an elevated fasting homocysteine level in the blood, their symptoms are likely not related to the MTHFR gene changes, but this should be discussed with your doctor.
  • Only the common polymorphisms have been studied with relationship to symptoms, but there are many other MTHFR gene changes that have not been studied.
  • Women with elevated homocysteine levels and two copies of the C677T polymorphism may be at a slight increased risk to have a child with a neural tube defect compared to women without these risk factors.
  • Women and men with elevated homocysteine levels and two copies of the C677T polymorphism may have a slight increased risk for venous thromboembolism (blood clots).
  • An individual’s risk for certain symptoms may be slightly increased by the presence of MTHFR polymorphisms, therefore, their overall risk is likely still quite low.
  • Symptoms studied may have been masked since certain countries have started a folate fortification program of all grain products, which may reduce the impact of MTHFR polymorphisms.

Testing for the MTHFR Gene Mutation

Technology has dramatically changed medicine in terms of diagnosis and our understanding of the human genome. Not long ago the catalyst behind many diseases was unknown.

Today we are able to use sophisticated yet simple tests to analyze genes that are responsible for a multitude of disorders.

Testing for the MTHFR gene variant is possible, but for many people, testing is not necessary and is actually not recommended 8.

Why Test for an MTHFR Mutation?

Although having an MTHFR variant is common, health risks are relatively small. Studies have shown inconclusive results.

Also, many of the symptoms that may be associated with MTHFR are probably caused by many genetic and environmental factors, not just the MTHFR polymorphisms. That’s why testing for MTHFR mutation isn’t a common practice.

It should be noted that health organizations don’t currently recommend MTHFR gene mutation testing as a part of standard screening for blood clots, pregnancy loss, or cardiovascular disease (CVD) 9.

This could change in the future as we learn more about how these mutations impact our lives.

If someone has an elevated fasting homocysteine level, they should discuss these symptoms with their doctor to discuss a full workup for the cause. If the homocysteine level is normal, it is unlikely that the MTHFR gene polymorphisms are to blame for the symptoms.

Different Ways to Test for MTHFR Gene Mutations

If you are still interested in MTHFR testing, there are a few ways to find out if you may have a polymorphism. Testing can be done to look for gene polymorphisms and identify which one(s) may be present.

How to Get a DNA Test for an MTHFR Mutation

In some cases, a physician will order a blood test to verify whether an MTHFR gene variant is present. This might be part of a larger evaluation and the blood work will be sent to a lab for analysis and will be examined for a wide variety of elements beyond the MTHFR gene.

Don’t have a medical condition that warrants a blood test? There are other MTHFR gene testing options available to consumers. However, they are not recommended by many health organizations.

Do At-home DNA Kits Test for the MTHFR Gene Mutation?

At home DNA test kits do not typically test for true Homocystinuria. If there are concerns for this condition, this should be discussed with a doctor or genetic counselor who is familiar with this condition.

Some at home DNA genetic testing kits now provide information on certain polymorphisms in the MTHFR gene. A few companies offer at home test kits:

My Home MTHFR - This at-home genetic testing kit offers MTHFR polymorphism detection. To collect a sample you must swab the inside of your cheek. The specimen is then shipped to the company’s lab for analysis. The results are available in just 1-2 weeks.

Which DNA Test is the Best Option?

A test through a physician is always going to be preferable.

Interpreting the DNA Test Results

Interpreting an MTHFR gene test could be difficult based on the conflicting research at this time.

YourDNA can connect you with specialists that are able to expertly interpret DNA testing results, including MTHFR gene variant tests.

Since DNA tesing is not typically recommended, treatment typically does not change for individuals with MTHFR gene polymorphisms.

Cost of Testing for MTHFR Gene Mutations

The cost of MTHFR gene testing depends on the method used.

The My Home MTHFR test costs $150.

Insurance Coverage for MTHFR Testing

In most cases, MTHFR gene mutation testing is not recommended for diagnosis or risk determination. Tests that aren’t ordered by a medical professional most likely won’t be covered by insurance.

It’s always best to call your insurer to verify copays and additional costs if you are unsure about a procedure’s coverage.

What to Do if an MTHFR Variant Is Found Following a DNA Test

Testing positive for a gene variant can leave you with a lot of questions. The next steps following a positive test for an MTHFR gene variant depends on the variant.

Those who test positive for an MTHFR variant should discuss the result with a genetics counselor or doctor who is familiar with the MTHFR gene.

This is a good idea whenever any gene variant is discovered.

Powered by Froala Editor

Referenced Sources

  1. Homocystinuria.
    Genetics Home Reference. Retrieved July 8, 2019.
  2. Bringing clarity to the role of MTHFR variants in neural tube defect prevention. Stover PJ, MacFarlane AJ, Field MS. Am J Clin Nutr. May 13, 2015; 101(6):1111-1112.
  3. Homocysteine and MTHFR Mutations. Circulation, 132(1).
    Moll, S., & Varga, E. A. 2015.
  4. Methylenetetrahydrofolate Reductase Deficiency. Dean L. Medical Genetics Summaries. NCBI; Last updated October 27, 2016.
  5. Association of the Maternal MTHFR C677T Polymorphism with Susceptibility to Neural Tube Defects in Offsprings: Evidence from 25 Case-Control Studies
    Lifeng Yan , Lin Zhao , Yan Long , Peng Zou, Guixiang Ji, Aihua Gu , Peng Zhao. 03 October 2012.
  6. Recommendations: Women & Folic Acid.
    CDC. 2018, October 30. Retrieved July 8, 2019.
  7. ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing. Hickey SE, Curry CJ, Toriello HV. Genet Med. February 2013; 15(2):153-156.
  8. MTHFR Gene Mutation: What You Need to Know. National Society of Genetic Counselors : Blogs : (n.d.). Retrieved June 26, 2019.
  9. MTHFR: Addressing Genetic Counseling Dilemmas Using Evidence-Based Literature. Levin, B. L., & Varga, E. Journal of Genetic Counseling, 25(5), 901–911. 2016.