Test Overview
Test Methodology

The entire coding sequences (exons plus 15 bp upstream and 15 bp downstream of each coding exon) of the targeted gene(s) is captured, sequenced using NGS and aligned to the human reference genome. A minimum NGS coverage of 20X is achieved for all coding exons +/- 5 bp, and a minimum coverage of 10X an additional 10 bp from +/- 6 bp through +/- 15 bp. A minimum coverage of 10X is achieved for all clinically significant promoter regions. Regions which do not meet these quality metrics are filled with targeted Sanger Sequencing. Variants in the targeted regions that are of potential clinical significance, based on the ACMGG guidelines for interpretation of sequence variants (Richards et al. Genet Med 17(5):405-524, 2015), will be reported. All reported variants of potential clinical significance will be confirmed by a different technology or platform.

Test Usage

To detect the presence of PTPN11, SOS1, KRAS2, and RAF1 mutations in patients with Noonan syndrome and for carrier testing in families with a known pathogenic mutation in these genes.

Reference Range *

Interpretive report provided.

* Reference ranges may change over time. Please refer to the original patient report when evaluating results.

Test Limitations

This analysis will not identify variants in the regulatory elements or deep intronic regions of PTPN11, SOS1, KRAS2, or RAF1 or other regions in the genome that are not included in this test. This assay may not detect large deletions or duplications and balanced translocations involving the targeted gene(s). As new scientific information becomes available, the interpretation and classification of variants identified in this assay may change. This information reflects the current state of scientific understanding at the time of test completion. Test interpretation may be impacted by diagnosis of a hematologic malignancy or an allogenic bone marrow transplant.

Test Details
Days Set Up
Monday - Friday
Analytic Time

28 days

Soft Order Code
MiChart Code
Noonan Syndrome Tiered Testing
  • Noonan Sequencing Panel
  • NSST1S
  • PTPN11(3ex)+SOS1(4ex)seqShadow
  • NSST1
  • PTPN11 (3 EX)+SOS1 (4 EX) SEQ
  • NSST2S
  • PTPN11(remaining ex)seq Shadow
  • NSST2
  • NSST3S
  • KRAS(5ex)+SOS1(19ex)seq Shadow
  • NSST3
  • KRAS (5 EX)+SOS1 (19 EX) SEQ
  • PTPN11 Mutation Analysis
  • SOS1 Mutation Analysis
  • KRAS2 Mutation Analysis
  • RAF1 Mutation Analysis
  • Noonan Syndrome Sequencing Panel
MMGL Molecular Genetics
Specimen Requirements
Collection Instructions

Collect specimen in a lavender top tube. Send intact specimen within 24 hours if stored at room temperature or within 5 days if stored refrigerated. Include the patient's family history, pedigree, and ethnicity on the test requisition. Obtaining informed consent from the patient prior to genetic testing is strongly recommended. If desired, a UMHS Request and Consent for Genetic Testing form can be obtained from the MMGL Molecular Genetics Laboratory by contacting the MLabs Client Services Center at 800-862-7284 or online at https://mlabs.umich.edu/media/188.

Normal Volume
5 - 10 mL EDTA whole blood
Minimum Volume
2 mL EDTA whole blood
Additional Information

This test is a reflexive assay consisting of 2 tiers. Tier 1 includes PTPN11. Tier 2 includes SOS1, RAF1 and KRAS. Testing will begin with Tier 1 and will be followed automatically by Tier 2 testing at an additional charge if no pathogenic mutations are found in Tier 1. Each Tier may also be ordered individually: indicate Tier 1 only (order code NSST1), Tier 2 only (order code NSST2).

CPT Code
Tier I: 81405; Tier II: 81406
Fee Code
Tier I: DA020; Tier II: DA021
Pro Fee CPT