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HelpEPIC CODE: LAB739 Methylenetetrahydrofolate Reductase (MTHFR) 2 Variants
Additional Codes
Sunquest: MTHFR
ARUP: 0055655
REGIONAL HOSPITAL PERFORMING
UnityPoint Health Methodist for processing
UnityPoint Health Pekin for processing
UnityPoint Health Proctor for processing
Performed at ARUP, Salt Lake City
Ordering Recommendations
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.
Collect
Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
Transport 3 mL whole blood. (Min: 1 mL)
Stability
Ambient: 72 hours; Refrigerated: 2 weeks; Frozen: 1 month
Unacceptable Conditions
Plasma or serum. Heparinized specimens.
Day(s) Performed
Sun-Sat
Duration of Testing
2-6 days
Methodology
Polymerase Chain Reaction and Fluorescence Monitoring
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 |
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.
This test was developed and its performance characteristics
determined by ARUP Laboratories. It has not been cleared or
approved by the US Food and Drug Administration. This test was
performed in a CLIA certified laboratory and is intended for
clinical purposes.
Counseling and informed consent are recommended for genetic
testing. Consent forms are available online.
Compliance Category
Laboratory Developed Test (LDT)
CPT
81291