Test ID: MTHFR
5,10-Methylenetetrahydrofolate Reductase C677T, Mutation, Blood
NY State Approved 
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Direct mutation analysis for the MTHFR C677T mutation should be reserved for patients with coronary artery disease, acute myocardial infarction, peripheral vascular artery disease, stroke, or venous thromboembolism who have increased basal homocysteine levels or an abnormal methionine-load test.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Direct Mutation Analysis
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
A223V Gene Mutation, Methylenetetrahydrofolate reductase
C677T Point Mutation
Methylenetetrahydrofolate Reductase 5,10
MTHFR A223V Gene Mutation
MTHFR Deficiency thermolabile type
reductase C677T point mutation
A223V Gene Mutation, MTHFR Deficiency
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Container/Tube:
Preferred: Yellow top (ACD solution B)
Acceptable: Lavender top (EDTA) or blue top (sodium citrate)
Specimen Volume: Full tube
Collection Instructions:
1. Invert several times to mix blood.
2. Send specimen in original tube.
Additional Information: Can be combined with other molecular coagulation tests:
-61730/MTHAC 5,10-Methylenetetrahydrofolate Reductase A1298C, Mutation, Blood
-81419/F5DNA Factor V Leiden (R506Q) Mutation, Blood
-81742/PTNT Prothrombin G20210A Mutation, Blood
-61367/MTHP 5,10-Methylenetetrahydrofolate Reductase C677T and A1298C Mutations, Blood
Forms:
1. Coagulation Patient Information Sheet (Supply T675) is available in Special Instructions
2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Gross OK |
| Lipemia | Mild OK; Gross OK |
| Icterus | NA |
| Other | Green top (heparin) tube |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Whole blood | Ambient (preferred) | 7 days |
| Frozen | 7 days | |
| Refrigerated | 7 days |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Hyperhomocysteinemia is an independent risk factor for coronary artery disease, acute myocardial infarction, peripheral arterial disease, stroke, and venous thromboembolism. Homocysteine is a sulfhydryl-containing amino acid formed as an intermediary during the conversion of methionine to cystathionine. Genetic or nutrition-related disturbances (eg, deficiency of vitamins B12, B6, and folic acid) may impair the transsulfuration or remethylation pathways of homocysteine metabolism and cause hyperhomocysteinemia. The enzyme MTHFR catalyzes reduction of 5,10-methylene tetrahydrofolate to 5-methyl tetrahydrofolate, the major form of folate in plasma; 5-methyl tetrahydrofolate serves as a methyl donor for remethylation of homocysteine to methionine. Patients with severe MTHFR deficiency (enzymatic activity 0%-20% of normal) develop homocysteinuria, a severe disorder with a wide range of associated clinical manifestations, including developmental delay, mental retardation, and premature vascular disease. Seven unique MTHFR mutations have been associated with homocysteinuria, all among patients who were either homozygous or compound heterozygotes for 1 or more of these mutations.
A milder deficiency of MTHFR, with approximately 50% residual enzyme activity and marked enzyme lability to heat inactivation, is associated with a cytosine to thymine mutation at nucleotide position 677 (C677->T), encoding for an alanine-223 to valine substitution (MTHFR C677T). Patients who are homozygous for the MTHFR C677T mutation may develop hyperhomocysteinemia, especially with concurrent deficiency of vitamins B12, B6 (pyridoxine), or folic acid. This mutation is quite common, with a carrier frequency of 31% to 39% (homozygote frequency 9%-17%) among the white North American population. The MTHFR C677T mutation test is a direct assay of patient leukocyte genomic DNA.
For suspected hyperhomocysteinemia, we recommend that a basal plasma homocysteine level be measured. Vitamin B12, B6, and folic acid levels should be measured in patients with hyperhomocysteinemia.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Negative
Interpretation Provides information to assist in interpretation of the test results
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
For Mayo Clinic patients, Cardiovascular, Vascular, Thrombophilia Center, Special Coagulation Clinic, and Medical Genetics consultations and counseling are available for questions regarding DNA diagnostic testing, test interpretation, and patient management, and may be especially helpful in complex cases.
The MTHFR C677T mutation test does not detect other causes of hyperhomocysteinemia, such as occur with other mutations within the MTHFR gene or the cystathionine beta-synthase gene. In addition, the MTHFR gene mutation may not be present when hyperhomocysteinemia is due to acquired disorders, such as deficiency of vitamins B12, B6, or folic acid; chronic renal failure; zinc deficiency; leukemia; psoriasis; or antifolate drug therapy.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Rees MM, Rodgers GM: Homocysteinemia: association of a metabolic disorder with vascular disease and thrombosis. Thromb Res 1993;71:337-359
2. Frosst P, Blom HF, Goyette P, et al: A candidate gene risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nature Genet 1995;10:111-113
3. Ma J, Stampfer MJ, Hennekens CH, et al: Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial infarction in US physician. Circulation 1996;94:2410-2416
4. Deloughery TG, Evans A, Sadeghi A, et al: Common mutation in methylenetetrahydrofolate reductase: correlation with homocysteine metabolism and late-onset vascular disease. Circulation 1996;94:3074-3078
5. Heit JA: Thrombophilia: clinical and laboratory assessment and management. In Consultative Hemostasis and Thrombosis. Fourth edition. Edited by CS Kitchens, BM Alving, CM Kessler. Saunders, 2012
Method Description Describes how the test is performed and provides a method-specific reference
The assay is a direct mutational analysis of patient leukocyte genomic DNA. A hybridization reaction of patient genomic DNA with mutant or wild type probes along with an Invader Oligo creates a complex that is recognized and cleaved by the enzyme, Cleavase. A cleavage fragment from this complex then incorporates into a secondary complex that also is recognized and cleaved by the Cleavase enzyme, releasing a fluorophore that is specific for either the wild-type or mutant sequence. The reaction is read on a fluorescence detector at 485/530 and 560/612 wavelengths. The ratios between the readings determines the allelic zygosity of the patient.(Invader, Third Wave Technologies, Madison, WI; Hall JG, Eis PS, Law SM, et al: Sensitive detection of DNA polymorphisms by the serial invasive signal amplification reaction. Proc Natl Acad Sci USA 2000;97:8272-8277)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Tuesday; 1 p.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81291-MTHFR (5,10-methylenetetrahydrofolate reductase) (eg, hereditary hypercoagulability) gene analysis, common variants (eg, 677T, 1298C)
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 21827 | Methylenetetrahydrofol Reduc Mut, B | 21709-1 |
| 21828 | MTHFR Interpretation | 69047-9 |
| 21830 | MTHFR Reviewed By | In Process |
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