ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing

Genet Med. 2013 Feb;15(2):153-6. doi: 10.1038/gim.2012.165. Epub 2013 Jan 3.


MTHFR polymorphism testing is frequently ordered by physicians as part of the clinical evaluation for thrombophilia. It was previously hypothesized that reduced enzyme activity of MTHFR led to mild hyperhomocysteinemia which led to an increased risk for venous thromboembolism, coronary heart disease, and recurrent pregnancy loss. Recent meta-analyses have disproven an association between hyperhomocysteinemia and risk for coronary heart disease and between MTHFR polymorphism status and risk for venous t-hromboembolism. There is growing evidence that MTHFR polymorphism testing has minimal clinical utility and, therefore should not be ordered as a part of a routine evaluation for thrombophilia.

MeSH terms

  • Coronary Disease / diagnosis
  • Coronary Disease / genetics
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing / standards*
  • Genetics, Medical / methods
  • Genetics, Medical / organization & administration
  • Genetics, Medical / standards*
  • Genomics / methods
  • Genomics / organization & administration
  • Genomics / standards*
  • Humans
  • Hyperhomocysteinemia / diagnosis
  • Hyperhomocysteinemia / genetics
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Polymorphism, Genetic
  • Practice Guidelines as Topic*
  • Risk Factors
  • Thrombophilia / diagnosis
  • Thrombophilia / genetics
  • United States
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / genetics


  • Methylenetetrahydrofolate Reductase (NADPH2)