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Disorders of Folate Metabolism and Transport Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
FOLR1 81479,81479
MTHFR 81479,81479
SLC46A1 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10121Genes x (3)81479 81479(x6) $990 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • McKenna Kyriss, PhD

Clinical Features and Genetics

Clinical Features

Folate compounds, also known as vitamin B9, play an important role in a number of cellular processes. This includes DNA synthesis, repair, methylation, and other one-carbon transfer reactions (Heales et al. 2016). Deficiency of folate transport or metabolism can lead to global and/or cerebral folate deficiency, which causes a number of clinical symptoms. These symptoms may be hematological (such as megaloblastic anemia), neurological (including, but not limited to, developmental delay, hypotonia, ataxia, spasticity, seizures, intellectual disability, behavioral and psychiatric symptoms) and/or immunological (for example, infection with unusual organisms and even immunological deficiency severe enough to mimic severe combined immune deficiency (SCID)) (Forges et al. 2010; Grapp et al. 2012; Diop-Bove et al. 2014; Watkins and Rosenblatt 2014; Froese et al. 2016). Biochemical analysis may reveal low levels of folate or 5-methyltetrahydrofolate (5-MTHF) in the serum and/or cerebrospinal fluid (Pérez-Dueñas et al. 2010; Diop-Bove et al. 2014). In addition, in some cases hyperhomocysteinemia and homocystinuria may be observed, potentially along with changes in S-adenosylhomocysteine, cystathionine, and/or methionine levels in the plasma (Watkins and Rosenblatt 2014; Froese et al. 2016). Onset of these disorders typically occurs in infancy or early childhood (Forges et al. 2010; Grapp et al. 2012; Diop-Bove et al. 2014).


Three genes known to cause deficiency of folate transport or metabolism (FOLR1, MTHFR and SLC46A1) are included in this test. Pathogenic variants in these genes cause cerebral folate deficiency, severe MTHFR deficiency, or hereditary folate malabsorption, respectively. All of these disorders are autosomal recessive. Pathogenic variants in the MTHFR gene are the most common genetic cause of folate metabolic errors, with over 100 reported causative variants linked to severe MTHFR deficiency in the literature to date. Pathogenic variants in the FOLR1 and SLC46A1 genes are less common, with close to 20 variants reported in each gene. The majority of reported pathogenic variants in these genes are missense, although nonsense, splicing, and small deletions and duplications have all been reported as well (Human Gene Mutation Database).

Please see individual test descriptions for information on the molecular biology of each gene.

Clinical Sensitivity - Sequencing with CNV PGxome

To date, nearly all reported MTHFR and SLC46A1 patients have had two pathogenic variants detectable via direct gene sequencing (Goyette et al. 1995; Kluijtmans et al. 1998; Sibani et al. 2000; Sibani et al. 2003; Zhao et al. 2007; Urreizti et al. 2010; Mahadeo et al. 2011; Shin et al. 2011; Diop-Bove et al. 2014; Burda et al. 2015). Based on these studies, a clinical sensitivity of ≥98% is expected for MTHFR and SLC46A1 patients.

FOLR1 was sequenced in 72 patients with low levels (<40nmol/l) of 5MTHF in cerebrospinal fluid. Pathogenic FOLR1 variants were identified in 10 (~14%) patients (Grapp et al. 2012). The authors noted that of the 14 patients that had extremely low CSF 5MTHF levels (<5nmol/l), 10 (~70%) had pathogenic FOLR1 variants.

To date, no large deletions or duplications have been reported in FOLR1 or MTHFR (Human Gene Mutation Database).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Please note that as recommended by the ACMG, ACOG and AHA, we do not offer testing specifically for the MTHFR common polymorphisms c.665C>T and c.1286A>C (also known as C677T and A1298C) due to the limited clinical utility of such testing (Hickey et al. 2013; Levin and Varga 2016).

Indications for Test

Patients with clinical features consistent with a disorder of folate transport or metabolism are good candidates for this test, as are those with biochemical test results consistent with these disorders, such as abnormal levels of folate in the serum and/or cerebrospinal fluid.


Official Gene Symbol OMIM ID
FOLR1 136430
MTHFR 607093
SLC46A1 611672
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test



  • Burda P. et al. 2015. Human Mutation. 36: 611-21. PubMed ID: 25736335
  • Diop-Bove N. et al. 2014. Hereditary Folate Malabsorption. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301716
  • Forges .T et al. 2010. Molecular Genetics and Metabolism. 100: 143-8. PubMed ID: 20356773
  • Froese D.S. et al. 2016. Human Mutation. 37: 427-38. PubMed ID: 26872964
  • Goyette P. et al. 1995. American Journal of Human Genetics. 56: 1052-9. PubMed ID: 7726158
  • Grapp M. et al. 2012. Brain. 135: 2022-2031. PubMed ID: 22586289
  • Heales S. et al. 2016. Abnormalities of CSF Neurotransmitters/Folates. In: Hollak C.E.M. and Lachmann R.H., editors. Inherited Metabolic Disease in Adults: A Clinical Guide. New York: Oxford University Press, p 541-551.
  • Hickey S.E. et al. 2013. Genetics in Medicine. 15: 153-6. PubMed ID: 23288205
  • Human Gene Mutation Database (Bio-base).
  • Kluijtmans L.A. et al. 1998. European Journal of Human Genetics. 6: 257-65. PubMed ID: 9781030
  • Levin B.L., Varga E. 2016. Journal of Genetic Counseling. 25: 901-11. PubMed ID: 27130656
  • Mahadeo K.M. et al. 2011. The Journal of Pediatrics. 159: 623-7.e1. PubMed ID: 21489556
  • Pérez-Dueñas B. et al. 2010. Journal of Inherited Metabolic Disease. 33: 795-802. PubMed ID: 20857335
  • Shin D.S. et al. 2011. Molecular Genetics and Metabolism. 103: 33-7. PubMed ID: 21333572
  • Sibani S. et al. 2000. Human Mutation. 15: 280-7. PubMed ID: 10679944
  • Sibani S. et al. 2003. Human Mutation. 21: 509-20. PubMed ID: 12673793
  • Urreizti R. et al. 2010. Clinical Genetics. 78: 441-8. PubMed ID: 20236116
  • Watkins and Rosenblatt. 2014. Inherited Disorders of Folate and Cobalamin Transport and Metabolism. In: Valle D, Beaudet A.L., Vogelstein B, et al., editors. New York, NY: McGraw-Hill. OMMBID.
  • Zhao R. et al. 2007. Blood. 110: 1147-52. PubMed ID: 17446347


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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