Sam is MTHFR compound heterozygous.
Sam carries one copy of C677T and one copy of A1298C in the MTHFR gene — the "compound heterozygous" genotype. Together they reduce MTHFR enzyme activity by roughly 40–50%, which slows the conversion of dietary folate into its active form. The internet has a lot of bad advice about MTHFR. Sam's report sticks to what the evidence actually supports.
Two MTHFR variants and the supporting cast.
MTHFR's two common variants act independently, and their combined effect on enzyme activity is the practical question. DeepDNA also checks downstream methylation-pathway genes.
Methylation: slower, not broken.
MTHFR converts dietary folate into 5-methyltetrahydrofolate — the form your body actually uses to build DNA, run methylation reactions, and recycle homocysteine into methionine. With two reduced-activity variants on opposite copies of the gene, Sam's enzyme runs at about half speed.
"This is not a disease. About 10% of the general population carries some compound-heterozygous MTHFR combination. The clinical picture for most carriers is unremarkable — slightly elevated homocysteine on average, easily corrected by adequate folate intake."
What the evidence does not support: MTHFR as a cause of generic fatigue, anxiety, or chronic illness; expensive "methylation panels"; or megadose methylfolate supplementation. Sam's report explicitly calls these out, with citations.
Three concrete things to do.
- Eat folate-rich food daily. Leafy greens, legumes, asparagus, citrus. Dietary folate is converted by MTHFR even at reduced activity — you just need consistent supply.
- If supplementing, methylfolate (5-MTHF) over folic acid. The active form bypasses MTHFR entirely. Standard doses only; megadoses are not evidence-backed.
- Watch B12 too. The downstream pathway is B12-dependent. Vegetarians and vegans with MTHFR variants benefit from B12 monitoring.
Sources cited in Sam's full report: ACMG Practice Guidelines on MTHFR testing 2013, ClinVar (rs1801133, rs1801131), Hickey et al. Mol Genet Metab 2013.