Noonan Syndrome via the SOS1 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
7207 SOS1 81406 81406,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7207SOS181406 81406, 81479 $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.

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

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 1000-2500 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 SOS1. To date, seven RAS/MAPK genes (PTPN11, SOS1, RAF1, KRAS, SHOC2, BRAF, and NRAS) have been involved in NS. SOS1 variants are the second most common cause of NS, and account for 10-13% of all cases genotyped (Roberts et al. Nat Genet 39:70-74, 2007; Tartaglia et al. Nat Genet 39:75-79, 2007; Zenker et al. J Med Genet 44:651-656, 2007; Allanson and Roberts,GeneReviews, 2011). About 50 missense variants and a few small deletions, insertions and indels were reported. 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 et al. Pediatrics 126:746-759, 2010).

Clinical Sensitivity - Sequencing with CNV PG-Select

This test will detect causative variants in ~ 16-20% of NS patients without PTPN11 variants (Roberts et al. Nat Genet 39:70-74, 2007; Tartaglia et al. Nat Genet 39:75-79, 2007).

Testing Strategy

This test provides full coverage of all coding exons of the SOS1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with a clinical diagnosis of NS who do not have PTPN11 variants. As the clinical features of cardio-facio-cutaneous syndrome and Costello syndrome overlap with NS, patients who test negative for the genes most commonly associated with those conditions are also candidates.

Gene

Official Gene Symbol OMIM ID
SOS1 182530
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Noonan Syndrome 4 AD 610733

Related Tests

Name
Comprehensive Cardiology Panel
Fetal Concerns Panel
Pan Cardiomyopathy 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
  • Roberts, A. E., et.al. (2007). "Germline gain-of-function mutations in SOS1 cause Noonan syndrome." Nat Genet 39(1): 70-4. PubMed ID: 17143285
  • 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
  • Tartaglia, M., et.al. (2007). "Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome." Nat Genet 39(1): 75-9. PubMed ID: 17143282
  • Zenker, M., et.al. (2007). "SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome." J Med Genet 44(10): 651-6. PubMed ID: 17586837

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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