Ordering Recommendation

Determines 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.

Mnemonic
MTHFR PCR
Methodology

Polymerase Chain Reaction and Fluorescence Monitoring

Performed

Sun-Sat

Reported

2-6 days

New York DOH Approval Status
This test is New York DOH approved.
Specimen Required
Patient Preparation
Collect

Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).

Specimen Preparation

Transport 3 mL whole blood. (Min: 1 mL)

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions

Plasma or serum. Heparinized specimens.

Remarks
Stability

Ambient: 72 hours; Refrigerated: 2 weeks; Frozen: 1 month

Reference Interval

Negative: Neither of the MTHFR variants tested, c.665C>T (previously designated C677T) and c.1286A>C (previously designated A1298C), were detected. Other causes of elevated homocysteine levels were not evaluated.

Interpretive Data

Background Information for Methylenetetrahydrofolate Reductase (MTHFR), 2 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.
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. 

Compliance Category

Laboratory Developed Test (LDT)

Note
Hotline History
N/A
CPT Codes

81291

Components
Component Test Code* Component Chart Name LOINC
0055657 MTHFR Mutation: c.665C>T 28005-7
0055658 MTHFR Mutation: c.1286A>C 28060-2
0055660 MTHFR Interpretation 21709-1
2001331 MTHFR PCR Specimen 31208-2
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • MTHFR
  • MTHFR DNA assay
Methylenetetrahydrofolate Reductase (MTHFR) 2 Variants