Methylenetetrahydrofolate Reductase (MTHFR) 2 Mutations
0055655
 
Ordering Recommendation
Do not use for neural tube defect risk assessment or for thrombophilia screening. Use to determine genetic cause for hyperhomocysteinemia.
Mnemonic
MTHFR PCR
Methodology
Polymerase Chain Reaction/Fluorescence Monitoring
Performed
Sun-Sat
Reported
2-7 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
 
Remarks
 
Stability
Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable  
Reference Interval
Effective February 18, 2014
Negative:
Neither of the common MTHFR gene mutations tested, c.665C>T and c.1286A>C, were detected. Other causes of elevated homocysteine levels, coronary heart disease, or thrombosis were not assessed. This genotype is associated with a normal folate metabolism.
Interpretive Data
Background Information for Methylenetetrahydrofolate Reductase (MTHFR) 2 Mutations:
Characteristics:
Mutations in the MTHFR gene (c.665C>T and c.1286A>C) correlate with reduced enzyme activity; however, only homozygotes for c.665C>T or compound heterozygotes for c.665C>T/c.1286A>C have significantly elevated plasma homocysteine levels and an increased risk for premature cardiovascular disease. These individuals may also show toxicity from medications (ie, methotrexate) that affect folate metabolism.
Incidence:
The allele frequency of c.665C>T is 0.35 in European Caucasians and 0.12 in African Americans. The allele frequency of c.1286A>C is 0.31 in European Caucasians and 0.15 in African Americans.
Inheritance:
Autosomal recessive.
Cause:
Homozygosity for MTHFR gene mutation c.665C>T or compound heterozygosity for c.665C>T/c.1286A>C.
Mutations Tested:
c.665C>T (previously c.677C>T); p.Ala222Val and c.1286A>C (previously c.1298A>C); p.Glu429Ala.
Clinical Sensitivity:
Undefined. Sensitivity is dependent upon multiple contributing factors.
Methodology:
PCR followed by fluorescent monitoring using hybridization probes.
Analytical Sensitivity & Specificity
: 99 percent.
Limitations:
Only the two MTHFR gene mutations (c.665C>T and c.1286A>C) will be targeted. Diagnostic errors can occur due to rare sequence variations.

This test is performed pursuant to an agreement with Roche Molecular Systems, Inc.
This test is performed pursuant to an agreement with Siemens Medical Solutions.



Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.

See Compliance Statement C: www.aruplab.com/CS
Note
CPT Code(s)
81291
Components
Component Test Code*Component Chart Name
0055657MTHFR Mutation: C665T
0055658MTHFR Mutation: A1286C
0055660MTHFR Interpretation
2001331MTHFR PCR Specimen
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, contact interface support at interface.support@aruplab.com.
Cross References
  • Hyperhomocystinemia, C677T and A1298C Mutations
  • MTHFR