Performed

Monday - Friday

Methodology

Real-Time Polymerase Chain Reaction

Reported

Routine: 12 - 14 days

Synonyms

  • Methylenetetrahydrofolate Reductase Variants
  • MTHFR Variants
  • MTHFR Polymorphisms
  • c.665C>T
  • C677T
  • c.1286A>C
  • A1298C
  • Human MTHFR Gene
  • Clinical Genomics

Performing Lab

Clinical Genomics

Turnaround Time

14 days

Add-on Eligibility

Yes, within 7 days of collection
*If DNA has been extracted previously for other Clinical Genomics tests, this is stored for 6 weeks and may qualify for add-on

Specimen Type

Blood

Specimen Volume

5 mL (Minimum: 1 mL)

Collection Container

EDTA Whole Blood Tube (Lavender Top Vacutainer)

Unacceptable Conditions

  1. Severely clotted or grossly hemolyzed specimens
  2. Specimens that have been improperly collected, stored, or transported
  • Specimens collected in preservatives other than EDTA
    • ACD tubes are accepted, but EDTA is preferred
  • Serum or plasma
  • Specimens that have been frozen
  • Commingled specimens
  1. Specimens in tubes that have been damaged or broken during transport
  2. Specimens with insufficient volume for testing
  3. Unlabeled or mislabeled specimens

Storage/Transport Temperature

Transport Instructions      
Collection Location Transport Temperature Processing Required Timeframe
ED/Inpatient Room Temperature None Specimen must be received by the lab within 3 days of collection
Laboratory/Outpatient/Off-Site Room Temperature None Specimen must be received by the lab within 3 days of collection

Storage: Refrigerated

Stability (from collection to initiation)

Stability:
Prior to Extraction:
  • Room Temperature: 3 days
  • Refrigerated: 7 days
  • Frozen: Unacceptable
Extracted DNA:
  • Room Temperature: Unacceptable
  • Refrigerated: Unacceptable
  • Frozen: Indefinitely

Laboratory Storage: 
  • Original Specimen: Refrigerated
  • Extracted DNA: Frozen
Laboratory Retention: 
  • Original Specimen: 6 weeks
  • Extracted DNA: 6 weeks

Collection Instructions

Labeling Instructions:
When labeling blood tubes, leave a small window visible for the lab to assess the fill volume and sample integrity. Ensure that the barcode is in the correct orientation.


Collection Instructions:
Follow the correct order of draw when collecting with additional orders and tube types:
     

Reference Interval

Not Detected: Negative for the MTHFR gene mutations tested, C677T and A1298C

Interpretive Data

Refer to report for result specific interpretation details.

Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in folate metabolism as a cofactor for re-methylation of homocysteine. The common MTHFR variants, c.665C>T (historically known as 677C>T) and c.1286A>C (historically known as 1298A>C) are associated with a reduced function enzyme. Reduced enzyme activity of MTHFR is a genetic risk factor for hyperhomocysteinemia, especially in the presence of low serum folate levels, however hyperhomocysteinemia is multifactorial involving a combination of genetic, physiologic and environmental factors. Clinical relevance may be associated with homozygosity for the c.665C>T variant when accompanied by elevated plasma homocysteine levels, however MTHFR variant testing in the evaluation of venous thromboembolism or recurrent pregnancy loss is not recommended by the American College of Medical Genetics and Genomics (ACMG). The c.665C>T allele frequency is 31% in the general population, however it varies by ethnicity (50% Hispanic, 34% European, 29% East Asian, 15% South Asian, 11% African); and homozygosity occurs in 11% of the general population (26% Hispanic, 12% European, 9% East Asian, 3% South Asian, 1% African).

Mutations in the MTHFR gene (c.665C>T and c.1286A>C) correlate with reduced enzyme activity; however, only homozygotes for c.665C>T who also have elevated homocysteine have a mildly increased risk (odds ratio of 1.27) for venous thromboembolism. MTHFR variant testing in the evaluation of venous thromboembolism or recurrent pregnancy loss is not recommended by the American College of Medical Genetics and Genomics (ACMG).

Incidence: For the c.665C>T allele, the general population allele frequency is 31% and homozygosity is 11%.

Inheritance: Autosomal Recessive

Cause: Homozygosity for MTHFR gene mutation c.665C>T

Mutations Tested: c.665C>T and c.1286A>C

Clinical Sensitivity: Undefined. Sensitivity is dependent upon multiple contributing factors.

Methodology: Polymerase chain reaction and fluorescence monitoring

Analytical Sensitivity & Specificity: 99% 

Limitations: Only the two MTHFR gene mutations (C677T and A1298C) will be targeted; rare diagnostic errors may occur due to primer site mutations.

This test was developed and its performance characteristics determined by the UC San Diego Health System Molecular Diagnostics Laboratory. It has not been cleared or approved by the US Food and Drug Administration. FDA clearance or approval is not required for clinical use. The result of this test should be interpreted using all relevant clinical data and should not be used alone for clinical diagnosis or patient management decisions. 
Ordering

Performed

Monday - Friday

Methodology

Real-Time Polymerase Chain Reaction

Reported

Routine: 12 - 14 days

Synonyms

  • Methylenetetrahydrofolate Reductase Variants
  • MTHFR Variants
  • MTHFR Polymorphisms
  • c.665C>T
  • C677T
  • c.1286A>C
  • A1298C
  • Human MTHFR Gene
  • Clinical Genomics

Performing Lab

Clinical Genomics

Turnaround Time

14 days

Add-on Eligibility

Yes, within 7 days of collection
*If DNA has been extracted previously for other Clinical Genomics tests, this is stored for 6 weeks and may qualify for add-on
Collection

Specimen Type

Blood

Specimen Volume

5 mL (Minimum: 1 mL)

Collection Container

EDTA Whole Blood Tube (Lavender Top Vacutainer)

Unacceptable Conditions

  1. Severely clotted or grossly hemolyzed specimens
  2. Specimens that have been improperly collected, stored, or transported
  • Specimens collected in preservatives other than EDTA
    • ACD tubes are accepted, but EDTA is preferred
  • Serum or plasma
  • Specimens that have been frozen
  • Commingled specimens
  1. Specimens in tubes that have been damaged or broken during transport
  2. Specimens with insufficient volume for testing
  3. Unlabeled or mislabeled specimens

Storage/Transport Temperature

Transport Instructions      
Collection Location Transport Temperature Processing Required Timeframe
ED/Inpatient Room Temperature None Specimen must be received by the lab within 3 days of collection
Laboratory/Outpatient/Off-Site Room Temperature None Specimen must be received by the lab within 3 days of collection

Storage: Refrigerated

Stability (from collection to initiation)

Stability:
Prior to Extraction:
  • Room Temperature: 3 days
  • Refrigerated: 7 days
  • Frozen: Unacceptable
Extracted DNA:
  • Room Temperature: Unacceptable
  • Refrigerated: Unacceptable
  • Frozen: Indefinitely

Laboratory Storage: 
  • Original Specimen: Refrigerated
  • Extracted DNA: Frozen
Laboratory Retention: 
  • Original Specimen: 6 weeks
  • Extracted DNA: 6 weeks

Collection Instructions

Labeling Instructions:
When labeling blood tubes, leave a small window visible for the lab to assess the fill volume and sample integrity. Ensure that the barcode is in the correct orientation.


Collection Instructions:
Follow the correct order of draw when collecting with additional orders and tube types:
     
Result Interpretation

Reference Interval

Not Detected: Negative for the MTHFR gene mutations tested, C677T and A1298C

Interpretive Data

Refer to report for result specific interpretation details.

Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in folate metabolism as a cofactor for re-methylation of homocysteine. The common MTHFR variants, c.665C>T (historically known as 677C>T) and c.1286A>C (historically known as 1298A>C) are associated with a reduced function enzyme. Reduced enzyme activity of MTHFR is a genetic risk factor for hyperhomocysteinemia, especially in the presence of low serum folate levels, however hyperhomocysteinemia is multifactorial involving a combination of genetic, physiologic and environmental factors. Clinical relevance may be associated with homozygosity for the c.665C>T variant when accompanied by elevated plasma homocysteine levels, however MTHFR variant testing in the evaluation of venous thromboembolism or recurrent pregnancy loss is not recommended by the American College of Medical Genetics and Genomics (ACMG). The c.665C>T allele frequency is 31% in the general population, however it varies by ethnicity (50% Hispanic, 34% European, 29% East Asian, 15% South Asian, 11% African); and homozygosity occurs in 11% of the general population (26% Hispanic, 12% European, 9% East Asian, 3% South Asian, 1% African).

Mutations in the MTHFR gene (c.665C>T and c.1286A>C) correlate with reduced enzyme activity; however, only homozygotes for c.665C>T who also have elevated homocysteine have a mildly increased risk (odds ratio of 1.27) for venous thromboembolism. MTHFR variant testing in the evaluation of venous thromboembolism or recurrent pregnancy loss is not recommended by the American College of Medical Genetics and Genomics (ACMG).

Incidence: For the c.665C>T allele, the general population allele frequency is 31% and homozygosity is 11%.

Inheritance: Autosomal Recessive

Cause: Homozygosity for MTHFR gene mutation c.665C>T

Mutations Tested: c.665C>T and c.1286A>C

Clinical Sensitivity: Undefined. Sensitivity is dependent upon multiple contributing factors.

Methodology: Polymerase chain reaction and fluorescence monitoring

Analytical Sensitivity & Specificity: 99% 

Limitations: Only the two MTHFR gene mutations (C677T and A1298C) will be targeted; rare diagnostic errors may occur due to primer site mutations.

This test was developed and its performance characteristics determined by the UC San Diego Health System Molecular Diagnostics Laboratory. It has not been cleared or approved by the US Food and Drug Administration. FDA clearance or approval is not required for clinical use. The result of this test should be interpreted using all relevant clinical data and should not be used alone for clinical diagnosis or patient management decisions. 

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