Test Directory

Test Code
5081
Test Name
Noonan Spectrum Disorder NGS Panel
CPT Codes
81442
Expected Turnaround Time
Typically 2 to 4 weeks from receipt of a sample in the laboratory. All cases involving ongoing pregnancies will be expedited.
Clinical Utility
Genetic analysis to provide a molecular diagnosis of this disorder. Recommended for individuals with a personal and/or family history of this disorder to ensure appropriate treatment and establish recurrence risk for family members.
Specimen and Container Info

Non-Prenatal Specimens


Preferred/Alternate

Specimen Type

Containers

Volume

Preferred Specimen Type

Whole Blood

Lavender Top (EDTA)

3 mL

Alternate Specimen Type

Genomic DNA

1.5 mL Tube

3 µg (at a concentration of at least 30 ng/µl), preferably in TE solution.

Alternate Specimen Type

Fibroblasts

T-25 Flasks

2 confluent T-25 flasks, filled to capacity

Alternate Specimen Type

Saliva (Whole blood is recommended for CNV)

DNA Self-Collection Kit or Oragene Saliva Collection Kit for Young Children

Follow kit instructions (www.dnagenotek.com)


Prenatal Specimens

Either specimen type below is acceptable.


Specimen Type

Containers

Volume

Cultured cells

T-25 Flasks

2 confluent T-25 flasks derived from amnio or CVS samples.

Genomic DNA

1.5 mL Tube

3 µg (at a concentration of at least 30 ng/µl), preferably in TE solution.


NOTE: For specimens from outside of North America, the preferred specimen type is Genomic DNA. HNL Genomics does not recommend shipping whole blood or cultured cells from any location other than the United States, Canada, or Mexico.

Transport Instructions
  • Transport at room temperature within 24 hours.
  • If the specimen cannot be transported to the lab within 24 hours, refrigerate for up to 72 hours.
  • Do not freeze or expose to extreme temperatures, refrigerate for up to 72 hours if cannot be transported to lab within 24 hours. 
Stability Requirements

Room Temperature

24 hours

Refrigerated

72 hours

Causes for Rejection
  • Improperly labeled specimen (minimum of two patient identifiers)
  • Inappropriate specimen type
  • Incomplete or incorrect test request form
  • Insufficient volume
  • Specimen has leaked in transit
  • Specimen without a test order
Methodology
Next Generation Sequencing and Copy Number Variation Analysis
Performing Location
Genomics - Snowdrift
Description

The Noonan spectrum disorders are a clinically overlapping group of developmental disorders caused by mutations in genes involved in the RAS-MAPK signaling pathway (RASopathies). Clinical features of these disorders include short stature, cardiovascular defects, developmental delays, characteristic facial features, cutaneous findings, and an increased risk for specific types of cancer. The disorders included on this panel are Noonan syndrome, LEOPARD syndrome, Cardio-facial-cutaneous syndrome, Costello syndrome, Noonan-like syndrome with loose anagen hair, NF1 related Noonan syndrome, Noonan-like syndrome with or without juvenile myelomonocytic leukemia, and Legius syndrome. Other RASopathies or phenotype-related diseases, such as hereditary gingival neurofibromatosis, neurofibromatosis 2, and Baraitser-Winter syndrome, are also included in this panel. All of these disorders are reported to be inherited in an autosomal dominant manner, although most cases are caused by de novo mutations.

The Noonan spectrum disorder NGS panel consists of twenty-five genes: A2ML1, ACTB, ACTG1, BRAF, CABIN1, CBL, HRAS, KRAS, LZTR1, MAP2K1, MAP2K2, NF1, NF2, NRAS, NSUN2, PPP1CB, PTPN11, RAF1, RASA2, RIT1, RRAS, SHOC2, SOS1, SOS2 and SPRED1.


Gene

Disorder

MIM

A2ML1

Noonan syndrome, A2MN1 related

-

ACTB

Baraitser-Winter syndrome 1 (BRWS1)

243310

ACTG1

Baraitser-Winter syndrome 2 (BRWS2)

614583

BRAF

Noonan syndrome 7 (NS7)

Cardiofaciocutaneous syndrome (CFC1)

LEOPARD syndrome 3 (LPRD3)

613706

115150

613707

CABIN1

Neurofibromatosis, CABIN1 related

Schwannomatosis, CABIN1 related

-

-

CBL

Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL)

Leukemia, juvenile myelomonocytic (JMML)

613563

607785

HRAS

Costello syndrome (CSTLO)

218040

KRAS

Noonan syndrome 3 (NS3)

Cardiofaciocutaneous syndrome 2 (CFC2)

RAS-associated autoimmune leukoproliferative disorder (RALD)

609942

615278

614470

LZTR1

Noonan syndrome 10 (NS10)

616564

MAP2K1

Cardiofaciocutaneous syndrome 3 (CFC3)

615279

MAP2K2

Cardiofaciocutaneous syndrome 4 (CFC4)

615280

NF1

Neurofibromatosis-Noonan syndrome (NFNS)

Neurofibromatosis, type 1 (NF1)

Neurofibromatosis, familial spinal (FSNF)

Leukemia, juvenile myelomonocytic (JMML)

601321

162200

162210

607785

NF2

Neurofibromatosis, type 2 (NF2)

Schwannomatosis (SWNTS1)

101000

162091

NRAS

Noonan syndrome 6 (NS6)

613224

NSUN2

Noonan syndrome-like disorder, NSUN2 related

-

PPP1CB

Noonan syndrome-like disorder with loose anagen hair 2 (NSLH2)

617506

PTPN11

Noonan syndrome 1 (NS1)

LEOPARD syndrome 1 (LPRD1)

163950

151100

RAF1

Noonan syndrome 5 (NS5)

LEOPARD syndrome 2 (LPRD2)

611553

611554

RASA2

Noonan syndrome, RASA2 related

-

RIT1

Noonan syndrome 8 (NS8)

615355

RRAS

Noonan syndrome-like disorder, RRAS related

-

SHOC2

Noonan syndrome-like disorder with loose anagen hair (NSLH)

607721

SOS1

Noonan syndrome 4 (NS4)

Fibromatosis, gingival, 1 (GINGF1)

610733

135300

SOS2

Noonan syndrome 9 (NS9)

601247

SPRED1

Legius syndrome

611431

Testing Schedule
Monday-Friday
Genes
MAP2K2, NRAS, PTPN11, NF1, ACTB, KRAS, LZTR1, RRAS, CBL, SOS1, CABIN1, SOS2, NSUN2, MAP2K1, ACTG1, RIT1, RAF1, NF2, PPP1CB, BRAF, SPRED1, SHOC2, HRAS, A2ML1, RASA2
MIM
615279, 616564, 613707, 615355, 601321, 613224, 611431, 613563, 611553, 611554, 151100, 218040, 615280, 601247, 607721, 615278, 610733, 613706, 115150, 163950, 609942
Disease Group
Cardiovascular Disorders, Dysmorphology, Craniosynostosis and Craniofacial Disorders