Additional Information

Ordering Recommendation: Examines one genetic factor that contributes to hyperhomocysteinemia. Test is not recommended for recurrent pregnancy loss, thrombophilia screening, or neural tube defect risk assessment, or for family members of individuals with known MTHFR variants. Characteristics: Variants in the MTHFR gene may reduce enzyme activity contributing to hyperhomocysteinemia. Although hyperhomocysteinemia was previously reported to be a risk factor for many conditions, especially venous thrombosis and cardiovascular disease, recent meta-analysis casts doubt on whether lifelong moderate homocysteine elevation has an effect on cardiovascular disease. The American College of Medical Genetics Practice Guidelines indicate that individuals with elevated homocysteine and two copies of the c.665C>T variant have an odds ratio of 1.27 for venous thromboembolism. Thus, they recommend MTHFR genotyping not be ordered as part of a routine evaluation for recurrent pregnancy loss or thrombophilia due to questionable clinical significance. Variants Tested: c.665C>T(p.Ala222Val) and c.1286A>C(p.Glu429Ala). (legacy names, C677T and A1298C, respectively).