Glycine N-Methyltransferase Deficiency via the GNMT Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11831 GNMT 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11831GNMT81479 81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information.

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

For Reflex to PGxome pricing click here.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

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

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Defects in the Glycine N-Methyltransferase (GNMT) enzyme have been shown to lead to persistent, isolated hypermethioninemia, which is the elevation of methionine in plasma without accompanying homocystinemia. This hypermethioninemia persists beyond the first months of life (Mudd et al. 2001). Very few patients have been described with defects in the GNMT enzyme. Clinically, the identified patients have presented with hepatomegaly (in one family) and chronic elevation of serum transaminases indicative of liver disease, but not attributable to typical causes of liver disease. Biochemically, all patients were found to have persistently elevated serum methionine levels with normal levels of plasma homocysteine, tyrosine and sarcosine. In addition, serum adenosylmethionine (AdoMet) was elevated while serum adenosylhomocysteine (AdoHcy) levels were normal (Mudd et al. 2001; Luka et al. 2002; Augoustides-Savvopoulou et al. 2003).

Onset appears to be during early childhood, although it is not currently known how early hypermethioninemia would be detected in GNMT deficient individuals. Due to the small number of cases reported, the long-term prognosis of the GNMT patients is currently unknown (Mudd et al. 2001; Luka et al. 2002; Augoustides-Savvopoulou et al. 2003).

Genetics

The Glycine N-Methyltransferase enzyme is encoded by the GNMT gene, located on chromosome 6 at 6p12. To date, only three GNMT deficient patients have been reported in the literature and thus far, inheritance appears to be autosomal recessive. Two of the patients were Italian siblings, who were each found to be compound heterozygous for the missense variants Leu49Pro and His177Asn (Luka et al. 2002). The third patient was of Greek origin, and was found to be homozygous for the missense variant Arg140Ser (Augoustides-Savvopoulou et al. 2003).

The GNMT enzyme is present in large amounts in liver, pancreas and prostate, and appears to be primarily a cytosolic enzyme. GNMT is involved in methionine metabolism. The enzyme methionine adenosyltransferase I/III converts methionine to adenosylmethionine (AdoMet), which is then converted to adenosylhomocysteine (AdoHcy) via the action of the GNMT enzyme. Mutations in the GNMT gene that affect activity of the GNMT enzyme lead to accumulation of methionine and AdoMet in the plasma (Mudd et al. 2001; Luka et al. 2009).

Clinical Sensitivity - Sequencing with CNV PGxome

At this time, the sensitivity of this test is difficult to estimate due to the low number of cases reported in the literature. Analytical sensitivity may be high as the only reported causative variants are detectable by sequencing (Luka et al. 2002; Augoustides-Savvopoulou et al. 2003).

Testing Strategy

This test provides full coverage of all coding exons of the GNMT gene 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 full coverage as >20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Patients with hypermethioninemia are good candidates for this test, particularly if they have elevated plasma AdoMet levels and normal plasma homocysteine, tyrosine and sarcosine levels. Family members of patients known to have GNMT variants are also good candidates, and we will also sequence the GNMT gene to determine carrier status.

Gene

Official Gene Symbol OMIM ID
GNMT 606628
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Glycine N-Methyltransferase Deficiency AR 606664

Citations

  • Augoustides-Savvopoulou et al. 2003. PubMed ID: 14739680
  • Luka et al. 2002. PubMed ID: 11810299
  • Luka et al. 2009. PubMed ID: 19483083
  • Mudd et al. 2001. PubMed ID: 11596649

Ordering/Specimens

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.

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


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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