Common MTHFR Mutations: A1298C & C677T

MTHFR is a gene in which many people have mutations, such as the most common: A1298C and C677T. Learn more from a mutant.

I hated the part of school when the alphabet was incorporated into math. Like…WHY? (Or Y? For all you math nerds.)

It was that familiar feeling that came over me when I learned that genetic mutations have names like A1298C or C677T. As if a topic like MTHFR isn’t complicated enough, we just have to name their mutations with numbers and letters as if it means anything to the average MTHFR.

If that’s you, let me set your mind at ease: you’re not alone. If you or someone you know has a MTHFR mutation, we’re in the same boat. Grab a paddle and let’s learn how to steer this thing toward better understanding.

MTHFR MUTATIONS

Assuming you’re already familiar with the basics of DNA and genes, a genetic polymorphism, otherwise known as a mutation, is simple to explain. (If you aren’t sure, this article may be a great precursor: MTHFR Explained: For Dummies.)

A discrepancy in the DNA code making up a gene is called a polymorphism. In the case of MTHFR, that can happen pretty often. Experts don’t have an exact number for all possible MTHFR mutations, but they do know that there are two that are very common: A1298C and C677T. 

COMMON MTHFR MUTATIONS SIMPLIFIED

Just like in an algebraic equation, there are individual parts to a mutation’s moniker. By breaking it down, we can simplify and better understand the whole. 

In mutations such as A1298C and C677T, numbers signify a position in the DNA sequence. Letters represent the code itself.

Do you remember anything about DNA bases? They are nucleotides that make up the rungs on the twisty ladder of DNA’s structure. Bases are: adenine (A), thymine (T), cytosine (C), and guanine (G). 

These bases make up the building blocks of a DNA code, and they interact with one another in sequences. Sequences are written in a specific order to accomplish their intended task.

Issues arise when bases are switched up.

The A and C in A1298C represents the switch from the natural adenine (A) to a cytosine (C) base at the 1298th position in the DNA’s code. The same goes for the C and T in C677T. Thymine (T) replaces cytosine (C) at position 677.

COMMON MTHFR MUTATION TYPES

Studying genetics teaches us that we have not one but two copies of each of our genes: one from each parent. So there are two parts to our MTHFR gene, two chances for it to form with or without mutations.

HETEROZYGOUS

If a person receives only one copy of a MTHFR gene with a mutation, they are heterozygous for that polymorphism.

(Ex: Dad has one mutation at the C677T position, Mom has one mutation at the A1298C position, but kid ends up with just one mutation at the A1298C position. Kid is heterozygous for the A1298C polymorphism.)

HOMOZYGOUS

If a person receives two copies of mutations at the same position, they are homozygous.

(Ex: Dad and Mom both have a mutation at the C677T position, and kid ends up with both bad copies. Kid is homozygous for the C677T polymorphism.)

COMPOUND HETEROZYGOUS

If a person receives one copy of a mutation at each position, they are compound heterozygous.

(Ex: Mom has a mutation at the C677T position, Dad has a mutation at the A1298C position, kid ends up with one mutation at the C677T position AND one mutation at the A1298C. Kid is compound heterozygous.)

It’s possible but highly uncommon for a person to have two copies of a mutation at one position as well as one at the other. Experts believe that this is because the effects of this genotype are so potent they may be deadly. They have yet to find anyone with two mutations at each position, which suggests that this is a fatal combination. 

MTHFR MUTATION FREQUENCIES & FACTORS

Remember when we said MTHFR mutations are common? In this case, common means that about 40% of the world has at least one somewhere in their genes. 

What’s interesting about MTHFR mutations is that they vary a lot by ethnicity, geography, and allele type. People of Hispanic and European descent seem to be the most prone, people of African descent the least. Parts of East Asia seem to have a higher population of mutations than in South Asia. In Italy, there are unusually high numbers of the C677T mutation.

It’s hard to determine exactly how many people have MTHFR mutations because of limited concrete results from genetic testing. Many U.S. health organizations discourage testing for MTHFR mutations without the presence of certain conditions, so numbers are estimated based on small research populations. 

Also, some mutations are studied more thoroughly than others, such as C677T. Out of the two common variants, A1298C is thought to have a milder effect on MTHFR enzymes than C677T, so there’s less information about it. Not to mention the many other possible—albeit rarer and mostly less affectatious—MTHFR mutations not at the 1298 or 677 positions that are largely ignored by current research.  

THE BOTTOM LINE

Even the most common MTHFR mutations, such as C677T and A1298C, are still in the throes of study. At the current rate of research, we may well know much more about them by the end of this decade. For my part and as a MTHFR, I can’t wait to learn more as our knowledge evolves thanks to hard work by dedicated geneticists, researchers, and healthcare professionals.

DISCLAIMER

I am not a healthcare professional. None of the content on this blog is meant to replace or substitute the advice of your doctor, nor should it be seen as health advice. Use your own good judgement and research to take what you will.

SOURCES

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630484/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10779094/
• https://evolution.berkeley.edu/dna-and-mutations/
• https://evolution.berkeley.edu/dna-and-mutations/dna-the-molecular-basis-of-mutations/
• https://www.cdc.gov/folic-acid/data-research/mthfr/
• https://link.springer.com/article/10.1007/s10916-020-01615-5

YOUR TURN

I’m homozygous for the C677T mutation. How about you? Drop it in the comments!