Determine genetic contribution to hyperhomocysteinemia for individuals with elevated plasma homocysteine. Not recommended for recurrent pregnancy loss, thrombophilia screening, neural tube defect risk assessment, or testing of family members of individuals with identified MTHFR variants.
- Patient Preparation
- Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Plasma or serum. Heparinized specimens.
- Ambient: 72 hours; Refrigerated: 2 weeks; Frozen: 1 month
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.
Incidence: The allele frequency of the c.665C>T variant is 0.35 in European Caucasians, 0.5 in Hispanics, and 0.12 in African Americans.
Inheritance: Autosomal recessive; two copies of the c.665C>T variant may be a contributing factor to hyperhomocysteinemia.
Variants Tested: c.665C>T(p.Ala222Val) and c.1286A>C(p.Glu429Ala). (legacy names, C677T and A1298C, respectively).
Clinical Sensitivity: Undefined; hyperhomocysteinemia is caused by genetic, physiologic and environmental factors. MTHFR variants are only one contributing factor.
Methodology: Polymerase chain reaction (PCR) and fluorescence monitoring.
Analytical Sensitivity & Specificity: 99 percent.
Limitations: Only two MTHFR gene variants (c.665C>T and c.1286A>C) are tested. Diagnostic errors can occur due to rare sequence variations.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|0055657||MTHFR Mutation: c.665C>T||28005-7|
|0055658||MTHFR Mutation: c.1286A>C||28060-2|
|2001331||MTHFR PCR Specimen||31208-2|
- MTHFR DNA assay