MTHFR – Beyond C677T and A1298C

Going beyond MTHFR 677 and 1298

The MTHFR C677T and A1298C variants get a lot of press  – from Facebook groups to whole websites that talk about them.  (If you don’t know your status on those two, check out this page: MTHFR)

But MTHFR C677T and A1298C are not the whole picture for this gene. There are additional variants that also impact the functionality of the enzyme.

MTHFR is a key gene in regulating the body’s folate metabolism. The folate cycle interacts with the methylation cycle, supplying the body’s need for methyl groups.

Other MTHFR Genetic Variants:

Other variants that decrease MTHFR enzyme function:

Check your genetic data for rs2274976 G1793A or R594Q (23andMe v4, v5; AncestryDNA) known as :

  • T/T: associated with cleft lip, OR 3.46 [ref] neural tube defect [ref], higher homocysteine, and folate deficiency [ref] increased risk of schizophrenia in children[ref][ref] cognitive issues possible for seniors with this genotype in conjunction with low vitamin B12[ref]
  • C/T: somewhat increased risk of schizophrenia, cognitive issues possible for seniors with this genotype in conjunction with low vitamin B12[ref]
  • C/C: typical


Variants that are associated with positive outcomes:

Check your genetic data for rs9651118 (23andMe v4; AncestryDNA):

  • T/T: most common genotype; relatively higher homocysteine, higher risk of T2D [ref],  [ref]
  • C/T: decreased risk of liver cancer [ref] slower cognitive decline in elderly[ref]
  • C/C: decreased risk of lung cancer [ref]


Check your genetic data for rs13306560 (23andMe v4; AncestryDNA):

  • A/A: avg 5.2 mmHg lower diastolic blood pressure [ref] Protective against Parkinson’s[ref]
  • A/G: avg 2.6 mmHg lower diastolic blood pressure
  • C/C: common



Foods that are high in folate include: [ref]

  • Beef liver
  • Lentils, black-eyed peas
  • Spinach
  • Broccoli
  • Avocados

If you don’t eat enough folate-rich foods on a regular basis, methylfolate supplements are also available. The RDA for folate is 400 mcg/day for adults (600 mcg/day for pregnancy).

Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.