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  • Writer's pictureNancy Mullan, MD

What About MTHFR A1298C? What Does That Do?

Updated: Jan 23, 2020

If you have a mutation in your MTHFR A1298C gene, your body is impacted very differently from a mutation at MTHFR C677T or MTHFR 03.

Most people mean MTHFR C677T when they refer to MTHFR, because it is a common  mutation and it has a major impact. But MTHFR A1298C is significant also.

MTHFR C677T and MTHFR 03 work in the same way.

Mutations in either of these genes slow down your MTHFR enzyme activity. MTHFR 03 generates the more profound slowdown of the two. As a result of either of these mutations, you produce less 5-methylfolate to convert homocysteine back into methionine, and as a result you produce fewer methyl groups. I have a downloadable, no-cost ebook available here that explains this process in Chapter 3.

But an MTHFR A1298C mutation works in an entirely different way from MTHFR C677T or MTHFR 03. MTHFR A1298C performs a regulatory function. It regulates the amount of SAMe, S-adenosyl methionine, you produce. SAMe is your body’s main methyl group supplier. So it regulates how many methyl groups you make in a less direct way. Your body needs not too many or not too few methyl groups. Their production is strictly regulated.

When the cycles are going in a forward direction, your body produces SAMe. If your level of SAMe gets too high, it signals a regulatory sensor at the MTHFR A1298C position. Triggering this sensor makes your body reverse the biochemical reaction, halting your production of SAMe and reducing your  number of methyl groups.

When you have a mutation at A1298C, your sensor is not as sensitive to the amount of SAMe surrounding your cells, and this regulation does not work as well. You may get an overload of methyl groups. You can get a number of symptoms. These differ from person to person. You can feel jittery, depressed, have mood swings, or feel like you have the flu. You feel terrible. This is a signal that one of your body’s major regulatory systems is out of balance. You can get the same problems by taking too many methyl donating supplements for your genetics, or by taking too much supplement too soon, if you have ever done that…

Beyond that, this cycle’s going in the reverse direction is important for the production of the neurotransmitters, so you may get an underproduction of dopamine and serotonin. You may get depressed or other symptoms commonly thought of as psychological.

Some of the problems caused by mutations in the MTHFR genes are not intuitively obvious.

It is not kitchen medicine. If you have significant health problems and you know or suspect that you have an MTHFR mutation, you need help. I am an MTHFR specialist with over ten years of experience with this gene and its consequences. I treat more MTHFR positive patients than any other doctor in the US.

Why stumble around in the dark? You can go for weeks trying a solution that is flat out wrong for you, and then try another one that doesn’t work any better. You end up feeling lost and desperate and like there is no hope. I help people just like you all the time.

I have a free, downloadable ebook that you can opt in for at that gives you further detail about these issues. Click here to get your free ebook.

Try an Exploratory Conversation with me.

In this 30 minute conversation, I will listen to your symptoms, look at the lab tests you email me, tell you what I think, and leave you feeling enlightened and relieved. What I tell you will make sense, that there is a path forward, that you have found a clinician who ‘gets it.’ My fee is $129 for this conversation. It is quick and easy and does not involve becoming a patient. I can clarify your confusion and pull you out of the muddle.

Email me at and ask for this time with me.

I look forward to being able to help, Dr. Nancy

What people like you are saying about Dr. Mullan’s work:

I shudder at the thought of what my family would be like without Dr. Mullan. Thankfully, with her help, we have stopped my husband's chronic 30 year battle with kidney stones. He is no longer forming them and is stone free. My thyroid is now working normally, my body temperature is almost normal and my hair has grown back. My oldest daughter's Autism is in the process of being reversed and her hair pulling has stopped. The greatest blessing from our good health is the birth of my second daughter Ava, now one-year-old. At 50 years old I carried her to term. One of my doctors commented to me saying “ you are carrying this baby like a 22-year-old.” Yes, I am because of Dr. Mullan and working on my methylation pathway. One by one she is knocking off symptoms and bringing us back to health. The future is bright! Thank you, Dr. Mullan, for the work you do.


Wow. I feel great. Thank you for your help. It's amazing really. Like a light turned on. Curious to see what the next tests show. To ride this peak indefinitely is my goal. Ha. I have energy again. Yay!

Really grateful,


I am so relieved. My daughter is doing SO WELL since we started with you! We have been to so many doctors and tried so many things.Now I can start working on my own program with you....


So excellent! I literally learn something every single time and I get clarification on things that have been lingering in my mind… VB

You are giving people a huge gift by empowering them… It’s about helping the patient become their own healer by taking them to a higher level of consciousness… AL

Thank you so much, Dr. Mullan. Thank you so, so much for everything you do. MS

Wow! I have to tell you, this was such an uplifting session. It’s so nice to hear good news, especially about a child. Anxiety, OCD and a host of other mental/psychiatric symptoms have been a huge hurdle for me. So to hear this story of all those awful symptoms totally going away is such a bright light for me!!!! TR

Fantastic, caring, smart, savvy doc. I worked with Dr. Mullan for a couple of years to help MTHFR mutations and their associating expressions! To say the least! She's brilliant. At that time she had weekly calls for her patients - free - where we could ask questions and she would reply. What doctors do this? She does. She's also an animal lover and is right on about the way she practices medicine. I highly recommend her. In good health!


"Dr. Nancy Mullan is a beautiful person. She is an expert in her field and has helped our family so much. I am very grateful to her. She came highly recommended and I know why. I would recommend her and her website for information re: healing from a genetic point of view. Thank you, Dr. Mullan, for everything.”


"Dr.Mullan has helped me with issues that I have struggled with for years. She is knowledgable and practical. I would recommend her to others.”


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1 Comment

Tracy Marinin Beaudry
Tracy Marinin Beaudry
Jan 21, 2020

What about using adaptogens for neurotransmitter balance with a 1298C?

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