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Warburg Micro Syndrome via the RAB3GAP1 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
10481 RAB3GAP1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
10481RAB3GAP181479 81479(x2) $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. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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 backbone).

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

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 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Dana Talsness, PhD

Clinical Features and Genetics

Clinical Features

Warburg micro syndrome is an autosomal recessive disorder characterized by ocular, neurologic and endocrine abnormalities. Initial clinical findings are typically ocular and include bilateral congenital cataracts, microphthalmia, microcornea, and atonic pupils. Brain malformations are often seen on MRI and include polymicrogyria (primarily of the frontal and parietal lobes), cortical atrophy, and hypogenesis of the corpus callosum. Other key findings include severe intellectual disability, optic nerve atrophy, cortical visual impairment, postnatal microcephaly (rarely congenital), short stature, and hypogonadism (Handley et al. 2012. PubMed ID: 23176487; Handley et al. 2013. PubMed ID: 23420520; Handley and Sheridan 2018. PubMed ID: 29300443).

Martsolf syndrome has many overlapping features with Warburg micro syndrome but is considered to be less severe, often with milder intellectual disability and microcephaly while lacking optic atrophy and cortical visual impairment (Handley et al. 2012. PubMed ID: 23176487). Warburg micro and Martsolf syndromes were initially considered to be distinct; however, following the discovery of the molecular causes of each it is now believed these two disorders represent opposite ends of the same clinical spectrum.

Genetics

Warburg micro syndrome is an autosomal recessive disorder with pathogenic variants described in four genes (RAB3GAP1, RAB3GAP2, RAB18, TBC1D20). The majority of individuals with Warburg micro syndrome have pathogenic variants in RAB3GAP1 (41%), followed by RAB3GAP2 (7%), RAB18 (5%) and TBC1D20 (~5-6%) (Handley et al. 2012. PubMed ID: 23176487; Liegel et al. 2013. PubMed ID: 24239381).

To date, approximately 60 pathogenic variants have been reported in RAB3GAP1 with nearly all being likely loss of function pathogenic variants (nonsense, splicing, frameshift, large deletions). Only three missense variants have been reported; however, Gerondopoulos and colleagues reported that two of these are also likely loss of function as they result in no RAB3GAP1 GEF activity (Gerondopoulos et al. 2014. PubMed ID: 24891604).

RAB18 is a member of the RAB family of the RAS superfamily of small GTPases. RAB18 is involved in a number of different intracellular trafficking processes. The activity of RAB18 is dependent upon its GTP/GDP bound state. This state is regulated by GEFs (guanine nucleotide exchange factors) and GAPs (GTPase-activating proteins). RAB3GAP, which consists of RAB3GAP1 and RAB3GAP2 subunits, has been shown to act as a GAP specific for RAB3 proteins; however, until recently the relationship between RAB18 and RAB3GAP was unknown. Recent data suggest that contrary to its name the RAB3GAP complex can also act as a GEF specific for RAB18 (Gerondopoulos et al. 2014. PubMed ID: 24891604).

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in RAB3GAP1 were found in 63/153 (41%) families with Warburg micro syndrome or Martsolf syndrome (Handley et al. 2013. PubMed ID: 23420520).

Testing Strategy

This test provides full coverage of all coding exons of the RAB3GAP1 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. 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).

Indications for Test

Candidates for testing include patients with a clinical phenotype consistent with Warburg micro or Martsolf syndromes. Carrier screening and prenatal testing is available for at risk individuals. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in RAB3GAP1.

Gene

Official Gene Symbol OMIM ID
RAB3GAP1 602536
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Warburg Micro Syndrome 1 AR 600118

Related Test

Name
Warburg Micro Syndrome Panel

Citations

  • Gerondopoulos et al. 2014. PubMed ID: 24891604
  • Handley and Sheridan 2018. PubMed ID: 29300443
  • Handley et al. 2012. PubMed ID: 23176487
  • Handley et al. 2013. PubMed ID: 23420520
  • Liegel et al. 2013. PubMed ID: 24239381

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.
  • 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


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


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.

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