DNA icon

Noonan Syndrome via the SOS2 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
SOS2 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4365SOS281479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

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

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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.


Genetic Counselors


  • Brett Deml, PhD

Clinical Features and Genetics

Clinical Features

Noonan Syndrome (NS) 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 prenatal lymphatic abnormalities such as nuchal translucency, cystic hygroma, bilateral chylothorax, pleural effusion and polyhydramnios. Intelligence is usually normal; however, learning disabilities may be present. NS is characterized by 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. The prevalence of NS is estimated at 1 in 1000 to 1 in 2,500 births worldwide (Allanson et al. 1985; Nisbet et al. 1999; van der Burgt 2007; Romano et al. 2010).


NS is caused by gain of function pathogenic variants in various genes within the RAS/MAPK pathway. Several RAS/MAPK genes (PTPN11, SOS1, RAF1, KRAS, SHOC2, BRAF, NRAS, MAP2K1, RIT1, CBL and LZTR1) have been shown to be involved in NS.

Recently, five different pathogenic germline missense variants in the SOS2 gene were reported in 6 unrelated patients affected with NS without detectable pathogenic variants in the remaining Noonan-related genes. Pathogenic variants occurred de novo in two patients; they co-segregated with NS in four families with a history of the disease (Yamamoto et al. 2015; Cordeddu et al. 2015). All pathogenic variants reported to date are located in the Dbl homology (DH) domain of the protein. Based on the available data, the clinical features of patients with SOS2 pathogenic variants are similar to that observed in patients with SOS1 pathogenic variants. These include ectodermal and cardiac involvement with keratosis pilaris, sparse scalp hair, pulmonary stenosis and septal defects. Height and intellectual development are normal.

The SOS2 gene encodes a RAS guanine nucleotide exchange factor. SOS2 pathogenic variants resulted in enhanced signaling (Cordeddu et al. 2015).

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in SOS2 were detected in ~1% of patients with Noonan syndrome (Yamamoto et al. 2015).

Testing Strategy

This test provides full coverage of all coding exons of the SOS2 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 without pathogenic variants in the remaining Noonan-related genes.

Symptoms of NS patients overlap with those for CardioFacioCutaneous Syndrome (CFCS) and Costello Syndrome (CS) patients. NS patients who test negative for mutations in (PTPN11, SOS1, RIT1, RAF1, KRAS, SHOC2, BRAF, NRAS and CLB may be candidates for CFCS (MAP2K1 and MAP2K2 genes) or CS (HRAS gene) testing. Conversely, CFCS or CS Syndrome patients who test negative for BRAF, MAP2K1, MAP2K2 and KRAS genes or HRAS, respectively, may be candidates for NS testing. A comprehensive NGS sequencing panel that includes genes that have been implicated in NS, CFCS and CS is available.


Official Gene Symbol OMIM ID
SOS2 601247
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Noonan Syndrome 9 AD 616559


  • Allanson J.E. et al. 1985. American Journal of Medical Genetics. 21: 507-14. PubMed ID: 4025385
  • Cordeddu V. et al. 2015. Human Mutation. 36: 1080-7. PubMed ID: 26173643
  • Nisbet D.L. et al. 1999. Prenatal Diagnosis. 19: 642-7. PubMed ID: 10419612
  • Romano A.A. et al. 2010. Pediatrics. 126: 746-59. PubMed ID: 20876176
  • van der Burgt I. 2007. Orphanet Journal of Rare Diseases. 2: 4. PubMed ID: 17222357
  • Yamamoto G.L. et al. 2015. Journal of Medical Genetics. 52: 413-21. PubMed ID: 25795793


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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

loading Loading... ×


An error has occurred while calculating the price. Please try again or contact us for assistance.

View Ordering Instructions

1) Select Test Method (Platform)

1) Select Test Type

2) Select Additional Test Options

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: loading
Patient Prompt Pay Price: loading
A patient prompt pay discount is available if payment is made by the patient and received prior to the time of reporting.
Show Patient Prompt Pay Price
Copy Text to Clipboard