Brugada Syndrome via the RANGRF 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
3977 RANGRF 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3977RANGRF81479 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Brugada syndrome (BrS) is a potentially life-threating arrhythmia disorder without structural abnormalities, characterized by dizziness, syncope, nocturnal agonal respiration and sudden death. The classic electrocardiographic findings associated with BrS include ST segment elevation in leads V1 to V3, right bundle branch block, first degree AV block, and intraventricular conduction delay. BrS is much more common in men than in women, and many people who have BrS remain asymptomatic. Symptoms usually manifest during adulthood, but they may appear any time between two days and 80 years of age (Antzelevitch et al. 2005). BrS is treatable with preventive measures such as reducing fever, avoiding certain medications and using implantable cardiac defibrillator when necessary (Francis et al. 2005).

Genetics

BrS is an autosomal dominant genetic disorder with variable expression, resulting from pathogenic variants within genes that encode cardiac ion channels. BrS is also referred to as a “cardiac channelopathy.” Pathogenic variants in 16 genes (CACNA1C, CACNB2, CACNA2D1, GPD1L, KCND3, KCNE3, KCNE5, KCNJ8, HCN4, RANGRF, SCN5A, SCN1B, SCN2B, SCN3B, SLMAP, and TRPM4) influencing sodium and calcium currents in the heart are associated with BrS and account for at least 26%-41% of cases of BrS (Kapplinger et al. 2010; Crotti et al. 2012). Most patients with BrS have inherited a disease-causing variant from a parent, as de novo pathogenic variants in BrS are rare (Hedley et al. 2009).

The RANGRF gene (RAN Guanine Nucleotide Release Factor) contains five exons and is located at chromosome 17p13.1. Human MOG1, encoded by RANGRF, binds to Ran-GTP complex and Ran (Ras-related GTPase) and is essential for the transport of protein and RNA in and out of the nucleus (Steggerda et al. 2000). The cardiac sodium channel Nav1.5 is critical for heart function. Human MOG1 also interacts with the cytoplasmic loop II of Nav1.5 and modulates the expression and function of sodium channel Nav1.5 (Wu et al. 2008). A RANGRF loss-of- function pathogenic variant is linked to the physiopathology of Brugada Syndrome (Kattygnarath et al. 2011). To date, the majority of reported pathogenic variants in the RANGRF gene have been missense or nonsense (Human Gene Mutation Database).

Testing Strategy

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

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity cannot be estimated because only a small number of patients have been reported. However, pathogenic variants in RANGRF appear to be a rare cause of disease. Analytical sensitivity should be high because all reported pathogenic variants thus far are detectable by sequencing.

Indications for Test

All patients with symptoms suggestive of Brugada syndrome are candidates for this test.

Gene

Official Gene Symbol OMIM ID
RANGRF 607954
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID

Related Test

Name
Comprehensive Cardiology Panel

Citations

  • Antzelevitch C. et al. 2005. Circulation. 111: 659-70. PubMed ID: 15655131
  • Crotti L. et al. 2012. Journal of the American College of Cardiology. 60: 1410-8. PubMed ID: 22840528
  • Francis J., Antzelevitch C. 2005. International journal of cardiology. 101: 173-8. PubMed ID: 15882659
  • Hedley P.L. et al. 2009. Human mutation. 30: 1256-66. PubMed ID: 19606473
  • Human Gene Mutation Database (Bio-base).
  • Kapplinger J.D. et al. 2010. Heart Rhythm. 7: 33-46. PubMed ID: 20129283
  • Kattygnarath D. et al. 2011. Circulation. Cardiovascular Genetics. 4: 261-8. PubMed ID: 21447824
  • Steggerda S.M., Paschal B.M. 2000. The Journal of Biological Chemistry. 275: 23175-80. PubMed ID: 10811801
  • Wu L. et al. 2008. The Journal of Biological Chemistry. 283: 6968-78. PubMed ID: 18184654

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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