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Laboratory Test Directory

NGS RASopathy Panel (Noonan Spectrum Disorders NGS Panel)

Components

Name Method Department Units
NGS RASopathy Panel (Noonan Spectrum Disorders) Next Generation Sequencing (NGS)
Sanger sequencing
DNA extraction
Molecular Genetics

Specimen Requirements

Whole blood

Container Type Container Size Specimen Volume
Preferred

Purple tube (EDTA)

4 mL 4 mL-8 mL
Stability

Room temperature - 24 hour(s)
Refrigerated - 72 hour(s)

Specimen Preparation

  • Do not centrifuge
  • Do not freeze

Reasons for Rejection

  • Clotted specimen
  • Frozen specimen
  • Wrong collection tube

Comments

Please click on the Lab Form Link in the Forms Section to print and complete the Genetic Test Requisition Form, as well as the Informed Consent Form for Next Generation Sequencing (NGS)-based Testing. Submission of BOTH the Requisition Form and the Informed Consent Form is REQUIRED. This test concurrently sequences and analyzes the follwing 14 genes associated with RASopathy disorders: PTPN11, SOS1, RAF1, KRAS, NRAS, SHOC2, BRAF, MAP2K1 (MEK1), MAP2K2 (MEK2), HRAS, CBL, NF1, SPRED1, and RIT1 genes. RIT1 sequencing will be done by Sanger sequencing, while the remaining 13 genes will be sequenced NGS. Any reportable variants identified by NGS (pathogenic variants and variants of unknown clinical significance) will be confirmed by Sanger sequencing. Noonan syndrome, Costello syndrome, cardio-facio-cutaneous (CFC) syndrome, and LEOPARD syndrome are related genetic disorders caused by mutations in the genes that encode proteins in RAS-mitogen-activated protein kinase (MAPK) signal transduction pathway, and these disorders as a group are referred as RASopathy disorders. These RASopathy disorders have molecular and phenotypic overlap; however, each also has a distinct set of defining characteristics. Noonan syndrome is caused by mutations in PTPN11 (50%), SOS1 (10%), KRAS (<5%), RAF1 (3%-17%), NRAS (1% or less), SHOC2 (1% or less), and RIT1 (5-10%). Costello syndrome is caused by mutations in HRAS (80%-90%) and KRAS (10%-15%). CFC syndrome is caused by mutations in BRAF (75%-80%), MAP2K1 (MEK1) and MAP2K2 (MEK2) (10%-15%), and KRAS (<5%). LEOPARD syndrome is caused by mutations in PTPN11 (90%) and RAF1 (<10%). Mutations in the CBL gene can cause Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia. Mutations in the NF1 gene can cause Neurofibromatosis-Noonan syndrome, while mutations in the SPRED1 gene can cause Legius syndrome; both of these disorders have features overlapping with Neurofibromatosis type 1 and Noonan syndrome. It is likely that one or more additional as yet undefined genes, possibly related to RAS-MAPK signal transduction, are associated with these disorders. Thus, a negative result does NOT rule out any given clinical diagnosis. Targeted mutation analysis is available for other family members when a proband mutation is known (see test code: FN).

Forms

Lab Form

CPT Code

  • 81442