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Noonan and RASopathies NGS Panel

Noonan and RASopathies NGS Panel

  • Panel Description
  • Test Description
  • CPT Codes
  • Resources

Panel Description

Diseases Targeted:
RASopathies
Overview:
RASopathies is the collective term for conditions caused by pathogenic variants in the RAS-MAPK signaling pathway. Many of these conditions are characterized by distinct facial features, congenital heart disease, skin abnormalities, ocular abnormalities, hypotonia, and joint hyperextensibility. As a whole, RASopathies are among the most common autosomal dominant conditions affecting approximately 1 in 1,000 individuals.

Noonan syndrome is the most common RASopathy. It causes bleeding problems, heart defects, particularly pulmonary valve stenosis, short stature, and unusual facial features. People with Noonan syndrome may also have developmental disabilities, hearing or vision problems, or lymphedema. Some signs of Noonan syndrome may be present at birth including cryptorchidism, wide-set pale blue eyes, micrognathia, and loose skin on the neck.

This panel includes genes associated with the RAS-MAPK pathway that are associated with Noonan syndrome, cardiofaciocutaneous syndrome, Costello syndrome, Noonan syndrome with multiple lentigines, neurofibromatosis type 1, and capillary malformation-arteriovenous malformation syndrome. For a comprehensive approach, the panel also includes genes associated with conditions important to the differential diagnosis, such as Aarskog-Scott syndrome, Baraitser-Winter syndrome, genitopatellar syndrome, and Takenouchi-Kosaki syndrome.

Who is this test for?
This panel may be appropriate for anyone with a personal or family history of Noonan syndrome or other RASopathies. Infants born with multiple congenital malformations and dysmorphic features may benefit from testing. Testing can also confirm or rule out RASopathies as an explanation for short stature, or developmental delay.

What are the potential benefits for my patient?
Features of Noonan syndrome and RASopathies are distinct but also overlap with other conditions. Genetic testing can help confirm or rule out a diagnosis to help guide the course of treatment.

Genetic testing for Noonan Syndrome and RASopathies can:
  • Establish or confirm the appropriate diagnosis
  • Identify risks for additional health-related symptoms
  • Assist in modifying lifestyle changes
  • Result in more personalized treatment and symptom management
  • Inform family members about their own risk factors
  • Connect patients to relevant resources & support
  • Provide options for family planning

Test Description

Print
Order Options:
  • Sequencing
  • Del/Dup
  • Rush / STAT
  • Exclude VUS
  • MCC
  • Duo/Trio
Turnaround Time:
3-5 weeks
Cost:
Call for details
Genes:
A2ML1, ACTB, ACTG1, BRAF, CBL, CCNK, CDC42, EPHB4, FGD1, HRAS, KAT6B, KRAS, LZTR1, MAP2K1, MAP2K2, MAP3K8, MRAS, NF1, NRAS, PPP1CB, PTPN11, RAF1, RASA1, RASA2, RIT1, RRAS, SASH1, SHOC2, SOS1, SOS2, SPRED1 ( 31 genes )
Coverage:
96% at 20x
Specimen Requirements:
Blood (two 4ml EDTA tubes, lavender top) or Extracted DNA (3ug in EB buffer) or Buccal Swab or Saliva (kits available upon request)
Test Limitations:
All sequencing technologies have limitations. This analysis is performed by Next Generation Sequencing (NGS) and is designed to examine coding regions and splicing junctions. Although next generation sequencing technologies and our bioinformatics analysis significantly reduce the contribution of pseudogene sequences or other highly-homologous sequences, these may still occasionally interfere with the technical ability of the assay to identify pathogenic variant alleles in both sequencing and deletion/duplication analyses. Sanger sequencing is used to confirm variants with low quality scores and to meet coverage standards. If ordered, deletion/duplication analysis can identify alterations of genomic regions which include one whole gene (buccal swab specimens and whole blood specimens) and are two or more contiguous exons in size (whole blood specimens only); single exon deletions or duplications may occasionally be identified, but are not routinely detected by this test. Identified putative deletions or duplications are confirmed by an orthogonal method (qPCR or MLPA). This assay will not detect certain types of genomic alterations which may cause disease such as, but not limited to, translocations or inversions, repeat expansions (eg. trinucleotides or hexanucleotides), alterations in most regulatory regions (promoter regions) or deep intronic regions (greater than 20bp from an exon). This assay is not designed or validated for the detection of somatic mosaicism or somatic mutations.

CPT Codes:
CPT Code 81405, 81408, 81479

NOTE:  The CPT codes listed on the website are in accordance with Current Procedural Terminology, a publication of the American Medical Association. CPT codes are provided here for the convenience of our clients. Clients who bill for services should make the final decision on which codes to use.

Resources

DescriptionDownload
Noonan Syndrome and RASopathies


References:
 - Rauen, K.A.The RASopathies. Annu Rev Genomics Hum Genet. 2013;14:355-69. doi: 10.1146/annurev-genom-091212-153523. Epub 2013 Jul 15. (2013)