MTHFR Mutations C677T and A1298C: Explained In Plain English

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MTHFR mutations are one of the most well-studied genetic variations that can affect diet and health
More specifically, the variation MTHFR C677T and A1298C.
This video helps to clarify what each of these are, and what they mean for your health.

MTHFR mutations are actually quite common, and researchers suspect there are at least 30 different types.

C677T and A1298C are the most well-studied and tested of the lot.

The number and letter sequence refers to what is known as a single nucleotide polymorphism or SNP.
The letters and numbers describe where these polymorphisms are and what they look like.

While a “normal” MTHFR gene would be C677C (c = cytosine), a mutation or polymorphism has made the gene C677T (t = thymine).
Carriers with a T on the gene may have MTHFR enzymes that are less efficient, hence the issues associated with an MTHFR mutation.

What about the terms heterozygous and homozygous, what do they mean?
In genetics, hetero- and homo- refers to the two letters on the gene (known scientifically as alleles).
Hetero means different, homo means same. To use an obvious example, it's the same if we are talking about heterosexuality or homosexuality.

For C677T the alleles are C and T, which are different and therefore heterozygous.
T677T is a homozygous mutation, as there are two copies of the same mutant allele (T). Annoyingly, this is typically referred to as 'homozygous C677T'.

Yep, now I can see how this can be very confusing.

There is also compound heterozygous, which is when you have one mutant allele on both the 677 and 1298 base positions.
For example, MTHFR C677T + MTHFR A1298C is a compound heterozygous mutation.

Ok so which type of MTHFR mutation is the most harmful?

Heterozygous A1298C is thought to be of minor consequence (if any), while heterozygous C677T may affect folate metabolism by up to 35% at worst.

Homozygous mutations, as well as Compound heterozgous are considered the most severe or “at risk”. Some researchers say homozygous mutations can inhibit MTHFR enyzme function by up to 70%.

This if course can have consequences for folate metabolism and conditions related to it such as folate deficiency and high homocysteine. If you want to learn more about this, as well as the most appropriate diet for you, check out some of my other videos or follow the links in this video's description.

Remember that MTHFR mutations don’t directly make you unwell. But they may cause an exaggerated response to poor diet or lifestyle choices that others can “get away with”.
So use this knowledge as a tool to make better decisions for your health.

If you enjoyed this please give it a thumbs up and a share, and if you'd like to know more about MTHFR mutations simply click the link in the description.

Dietitian: Joe Leech (MSc Nutrition)