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Noonan Syndrome via the NRAS Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
9137 NRAS 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9137NRAS81479 81479(x2) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

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

  • Brett Deml, PhD

Clinical Features and Genetics

Clinical Features

Noonan syndrome (NS, OMIM 163950) is a relatively common developmental disorder that is characterized by dysmorphic facial features, growth and congenital heart defects, and musculoskeletal abnormalities. Cardiac abnormalities are found in up to 80% of patients and include pulmonary valve stenosis, atrial septal defect, atrioventricular canal defect, and hypertrophic cardiomyopathy. Musculoskeletal abnormalities include short stature, chest deformity with sunken or raised sternum, and short webbed neck. Several additional abnormalities have been described and include renal, genital, hematological, neurologic, cognitive, behavioral, gastrointestinal, dental, and lymphatic findings. Intelligence is usually normal; however, learning disabilities may be present. NS is characterized by an extensive clinical heterogeneity, even among members of the same family. Diagnosis is often made in infancy or early childhood. Symptoms often change and lessen with advancing age. Infants with NS are at risk of developing juvenile myelomonocytic leukemia (JMML OMIM 607785). The prevalence of NS is estimated at 1 in 1000 to 1 in 2500 births worldwide (Allanson et al. Am J Med Genet 21:507-514, 1985; Romano et al. Pediatrics 126:746-759, 2010).

Genetics

NS is caused by gain of function variants in various genes within the RAS/MAPK pathway, including NRAS. These variants appear to activate the gene product (SHP2 protein). To date, seven RAS/MAPK genes (PTPN11, SOS1, RAF1, KRAS, SHOC2, BRAF, and NRAS) have been involved in patients with NS. NRAS variants are a rare cause of NS and account for less than 1% of all cases genotyped (Allanson and Roberts, GeneReview, 2011). Three germline missense variants have been reported to date. Although de novo variants are found in a substantial fraction of patients, familial cases have been reported. In these families, NS is inherited in an autosomal dominant manner with variable expressivity (Romano, Pediatrics 126:746-59, 2010). Somatic NRAS variants have been implicated in JMML (Flotho et al. Leukemia 13:32-37, 1999). The NRAS gene encodes a small GTP-binding protein that is involved in cellular signal transduction.

Clinical Sensitivity - Sequencing with CNV PG-Select

This test will detect causative variants in less than 1% of NS patients.

Testing Strategy

This test provides full coverage of all coding exons of the NRAS gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Patients with clinical diagnosis of NS without variants in the genes that are commonly mutated in this disorder.

Gene

Official Gene Symbol OMIM ID
NRAS 164790
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Noonan Syndrome 6 AD 613224

Related Tests

Name
Autoimmune Lymphoproliferative Syndrome/ALPS Panel
Comprehensive Cardiology Panel
Fetal Concerns Panel
Sudden Cardiac Arrest Panel

Citations

  • Allanson JE, Hall JG, Hughes HE, Preus M, Witt RD. 1985. Noonan syndrome: the changing phenotype. Am. J. Med. Genet. 21: 507-514. PubMed ID: 4025385
  • Allanson, Judith E MD , Roberts, Amy E MD. (2011). "Noonan Syndrome." PubMed ID: 20301303
  • Flotho C, Valcamonica S, Mach-Pascual S, Schmahl G, Corral L, Ritterbach J, Hasle H, Aricò M, Biondi A, Niemeyer CM. 1999. RAS mutations and clonality analysis in children with juvenile myelomonocytic leukemia (JMML). Leukemia 13: 32–37. PubMed ID: 10049057
  • Romano AA, Allanson JE, Dahlgren J, Gelb BD, Hall B, Pierpont ME, Roberts AE, Robinson W, Takemoto CM, Noonan JA. 2010. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics 126: 746-759. PubMed ID: 20876176

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

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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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