Methylenetetrahydrofolate Reductase (MTHFR) Thermolabile Variant, DNA Analysis

CPT 81291
Synonyms
  • Hyperhomocysteinemia, C677T and A1298C Mutations
  • MTHFR

Test Details

Use

Follow-up evaluation in individuals with hyperhomocysteinemia

Limitations

Variants Analyzed: c.665C>T (p. Ala222Val), legacy name: C677T; and c.1286A>C (p. Glu429Ala), legacy name: A1298C. Results must be combined with clinical information for the most accurate interpretation. Molecular-based testing is highly accurate, but as in any laboratory test, diagnostic errors may occur. False positive or false negative results may occur for reasons that include genetic variants, blood transfusions, bone marrow transplantation, somatic or tissue-specific mosaicism, mislabeled samples, or erroneous representation of family relationships.

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

Methodology

Polymerase chain reaction (PCR) and restriction enzyme analysis

References

American College of Obstetricians and Gynecologists' Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 197: Inherited Thrombophilias in Pregnancy. Obstet Gynecol. 2018 Jul;132(1):e18-e34.29939939
Erratum in ACOG Practice Bulletin No. 197: Inherited Thrombophilias in Pregnancy: Correction.30247353
Hickey SE, Curry CJ, Toriello HV. ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing. Genet Med. 2013 Feb;15(2):153-156.23288205

Additional Information

Hyperhomocysteinemia is multifactorial, involving genetic, clinical, and environmental risk factors. Reduced enzyme activity of methylenetetrahydrofolate reductase (MTHFR) is a genetic risk factor for hyperhomocysteinemia, particularly when serum folate levels are low. There are two common variants in the MTHFR gene that can decrease enzyme activity: c.665C>T (p. Ala222Val), legacy name C677T, and c.1286A>C (p. Glu429Ala), legacy name A1298C. These variants do not independently increase risk of conditions related to hyperhomocysteinemia in the absence of elevated homocysteine levels. Measurement of total plasma homocysteine is recommended. Patients should share their MTHFR genotype with physicians who are making decisions regarding chemotherapy treatments that depend on folate, such as methotrexate. Guidelines do not recommend genotyping of these two MTHFR variants in the evaluation of venous thromboembolism or obstetric risk due to limited evidence of clinical utility. Genetic coordinators are available for health care providers to discuss results and for information on how to order additional testing, if desired, at 1-800-345-GENE.

Specimen Requirements

Information on collection, storage, and volume

Specimen

Whole blood or LabCorp buccal swab kit (buccal swab collection kit contains instructions for use of a buccal swab)

Volume

7 mL whole blood or LabCorp buccal swab kit

Minimum Volume

3 mL whole blood or two buccal swabs

Container

Lavender-top (EDTA) tube, yellow-top (ACD) tube, or LabCorp buccal swab kit

Storage Instructions

Maintain specimen at room temperature or refrigerate.

Causes for Rejection

Frozen specimen; hemolysis; quantity not sufficient for analysis; improper container; one buccal swab; wet buccal swab