Which is it!? MTHFR Mutation or MTHFR Polymorphism or MTHFR Defect?

MTHFR issue. What is the proper terminology?

MTHFR Mutation Naming Issue. Who's Right?

There is a lot of talk out there and it is causing confusion.

It is also causing arguments.

I’m hoping this post will cease the ‘I’m right!’ ‘No, I’m right!’ no winner type arguments.

People are calling the MTHFR issue many different things:


  • MTHFR Mutation
  • MTHFR Polymorphism
  • MTHFR Defect
  • MTHFR SNP (snips)
  • MTHFR Sequence Change
  • MTHFR Genetic Variant
  • MTHFR Gene Mutation
  • MTHFR Gene Polymorphism

Which one is it!?
Well – they are all pretty much right unfortunately. Unfortunately because it means we are changing our genes and passing the messed up MTHFR gene defect onto our kids who are also passing it onto their kids.

Autism on the rise? Hmmm. Wonder why.

Before I get into this, there are some terms you need to understand:
deleterious: injurious to health and cause health problems
benign: not injurious to health and don’t cause any health problems
bp: base pair
polymorphism: many ‘morphs’, the occurrence of more than one form.
nucleotide: make up the structural components of DNA and RNA. For our use, we are talking about the DNA nucleotides. There are four DNA nucleotides which are: Guanine, Cytosine, Thymine and Adenine

I’m sure a geneticist will smack me upside the head for saying that but I’ve got some support here from a published book on MTHFR Polymorphisms:

Mutation, polymorphism, variant and sequence change – these terms are used interchangeably…to denote the 677C -> T nucleotide substitution.
A mutation refers to any nucleotide change [Cytosine to Thymine, in this case]; a mutation can be benign or deleterious.
A polymorphism is simply a mutation that is common in the population ( > 1% prevalence); a polymorphism can be benign or deleterious.
All the above terminologies are therefore correct when discussing the substitution at bp 677. [bp = basepair] (1)

Let’s define some others and see if they appear correct:

  • SNP: single nucleotide polymorphism.  We have the MTHFR gene, which is 20,370 basepairs long (3), and at position 677 in the gene, we have a single nucleotide polymorphism (because it is common in the population). The single nucleotide polymorphism here is the Cytosine being switched by accident to a Thymine. Oops. Big Oops. Therefore, MTHFR SNP is correct.
  • Genetic Variant: Now this gets more complicated as there are many variations of variant. True, I’m afraid. A genetic variation is caused by variation in the order of bases in the nucleotides in genes.(2)  In MTHFR gene, position 677, we have a Thymine instead of a Cytosine. Yes. Genetic Variation is correct in my book. Expert geneticists disagree with me here? Please comment below. I’ll stand corrected.
  • Phenotypic Variation: As I said, there are variations to variant. Phenotypic variation includes a change in the order of nucleotides but it also includes a shape change of the gene. Anytime there is a change in shape, there is a change of function. Obviously, we have dysfunction in the MTHFR gene at position 677 when Cytosine changes to Thymine. We also have dysfunction when we have Adenine changing to Thymine. But do we have an actual shape change? According to research, yes – MTHFR is a phenotypic variation. It takes some digging and deeper understanding of what you’re reading, but the bottom line – MTHFR and Phenotypic Variants is accurate. Phenotypic variants are also scary – and so are genetic variants. More on this later…

So, it is like driving home from the store. You can take many different roads – each with a different name, but you’ll end up at the same destination.

Stop your arguing about it! :)

Dr Ben

(1) MTHFR Polymorphisms and Disease, page 13.
(2) Genetic Variation. Wikipedia (sorry – but it is quite a good explanation.)
(3) MTHFR, National Library of Medicine

4 Responses to “Which is it!? MTHFR Mutation or MTHFR Polymorphism or MTHFR Defect?”

  1. Jenny October 9, 2011 at 8:44 am # Reply

    Hello Dr. Ben,

    My lab report reads as follows: “MTHFR: two mutations (C677T and A1298C) identified.” (One copy of each mutation was identified.)
    Does this mean I have MTHFR polymorphism? There was nothing on the lab report about heterozygous or homozygous, so I am not sure where I stand.
    Also, my blood type is AB+, which is the rarest blood type. Does this factor in somehow?

    Thank you for the time and dedication you put into this website! It’s incredibly helpful!


    • Dr Ben October 12, 2011 at 1:50 am # Reply

      Jenny –

      Thank you for your comment and your praise ;) Always great to hear.

      You may what is called: Compound Heterozygous MTHFR mutation.

      This can be a fairly serious mutation and does require appropriate intervention.

      I am happy to provide individualized information should you desire it. You may schedule a consult here if you’d like:

      In terms of AB+ being relevant or not with compound heterozygous MTHFR mutations – I have not seen anywhere where this mutation would play a role in AB+ blood types.
      It may or may not but I personally don’t think so.

      In health,
      Dr Ben

  2. Amanda August 14, 2014 at 6:22 am # Reply

    When you say, “we are changing our genes and passing the messed up MTHFR gene defect onto our kids who are also passing it onto their kids,” I wonder if you could go more in depth about how we are changing our genes? Could you give us an example or two maybe?

    • Amanda August 14, 2014 at 6:24 am # Reply

      I can’t believe I just asked you a question without even saying thank you for all you do. Dr. Ben you have made an amazing impact on understanding MTHFR. Thank you!

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