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 Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 7207 | SOS1 | 81406 | 81406,81479 | $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.
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 Test
| Name |
|---|
| Comprehensive Arrhythmia and 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.
- 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
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ORDER OPTIONS
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2) Select Additional Test Options
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