Non-NF1 RASopathy NGS Panel - Clinical Genetic Test - GTR

Genetic Testing Registry

View Advanced Search Options

Classic view of this page

Non-NF1 RASopathy NGS Panel

Clinical Genetic Test

offered by

UAB Medical Genomics Laboratory

View lab's test page

GTR Test Accession: GTR000551628.6

INHERITED DISEASEMUSCULOSKELETALCARDIOVASCULAR ... View more

Last updated in GTR: 2023-06-07

Last annual review date for the lab: 2023-06-07 Past due

At a Glance

Test purpose:

Diagnosis

Conditions (7):

Noonan syndrome; Cardiofaciocutaneous syndrome 1; Costello syndrome more...

Genes (17):

BRAF (7q34); CBL (11q23.3); HRAS (11p15.5); KRAS (12p12.1); LZTR1 (22q11.21) more...

Methods (2):

Molecular Genetics - Deletion/duplication analysis: Multiplex Ligation-dependent Probe Amplification (MLPA); ...

Target population:

Patients with clinical features suggestive of either NS, NSML, CFC, …

Clinical validity:

Not provided

Clinical utility:

Establish or confirm diagnosis

Ordering Information

Offered by:

UAB Medical Genomics Laboratory
View lab's website
View lab's test page

Test short name:

NNP-NG

Specimen Source:

Cord blood
Fresh tissue
Frozen tissue
Isolated DNA
Peripheral (whole) blood
Saliva
Skin
View specimen requirements

Who can order:

Genetic Counselor
Health Care Provider
Licensed Physician
Nurse Practitioner
Physician Assistant

Test Order Code:

NNP-NG
View other test codes

CPT codes:

81442
81479

**AMA CPT codes notice

Lab contact:

Brandon Shaw, MS, CGC, Certified Genetic counselor, CGC, Genetic Counselor
brandonshaw@uabmc.edu
205-934-1520

Contact Policy:

Pre-test email/phone consultation regarding genetic test results and interpretation is provided to patients/families.

How to Order:

Additional information regarding the specific details needed for test submission can be found on our website
Order URL

Test service:

Clinical Testing/Confirmation of Mutations Identified Previously
Custom Deletion/Duplication Testing
Result interpretation

Informed consent required:

Based on applicable state law

Test strategy:

The Non-NF1 Rasopathy panel by NGS involves the simultaneous sequencing of 17 genes: SPRED1, PTPN11, PPP1CB, BRAF, CBL, HRAS, KRAS, LZTR1, NRAS, MAP2K1, MAP2K2, RAF1, RIT1, RASA2, SHOC2, SOS1 and SOS2. The test uses a customized and optimized set of Agilent Haloplex capture probes, followed by sequencing of overlapping amplicons … The Non-NF1 Rasopathy panel by NGS involves the simultaneous sequencing of 17 genes: SPRED1, PTPN11, PPP1CB, BRAF, CBL, HRAS, KRAS, LZTR1, NRAS, MAP2K1, MAP2K2, RAF1, RIT1, RASA2, SHOC2, SOS1 and SOS2. The test uses a customized and optimized set of Agilent Haloplex capture probes, followed by sequencing of overlapping amplicons within the regions of interest using Illumina sequencing chemistry. Each coding exon plus ~50bp of flanking intronic sequence are simultaneously sequenced. 5’ and 3’ untranslated sequences are not included. The average coverage is >2000x with >98.5% of the coding region ≥350x and 99.3% ≥200x, allowing detection of very low-level mosaicism, down to 3-5% variant allele fraction respectively (regions covered by ≥350x respectively ≥200x) with 95% confidence. The minimum coverage for any additional areas is >30x.
Variant and copy number calls are made using a unique bioinformatics pipeline detecting all types of mutations including single nucleotide substitutions, indels, and frameshifts caused by deletion/ duplication up to 112bp. Deletion/duplication analysis for LZTR1 and SPRED1 is included in this test, as such mutations are a part of the mutation spectrum for these conditions. Deletion/duplication analysis for the other 15 genes on this panel is not offered as current empirical and biological evidence is not sufficient to allow the conclusion that an altered copy number of these genes is a mechanism critical for the phenotype associated with the Rasopathies. Nevertheless, deletion/duplication analysis through aCGH analysis can be offered as a reflex test through the UAB cytogenetic laboratory (directed by Drs. A. Carroll and F. Mikhail).
Relevant family members of a proband with any (novel or previously identified) variant of unknown significance are offered free of charge targeted analysis as long as accurate phenotypic data are provided by a health care professional to enhance the interpretation. There is no limitation to the number of relatives that can be tested free of charge. View more

Pre-test genetic counseling required:

Decline to answer

Post-test genetic counseling required:

Decline to answer

Recommended fields not provided:

Test development

Conditions

Total conditions: 7

Condition/Phenotype	Identifier

Test Targets

Genes

Total genes: 17

Gene	Associated Condition	Germline or Somatic	Allele (Lab-provided)	Variant in NCBI

Methodology

Total methods: 2

Method Category

Test method

Instrument

Deletion/duplication analysis

Multiplex Ligation-dependent Probe Amplification (MLPA)

Applied Biosystems 3730 capillary sequencing instrument

Sequence analysis of the entire coding region

Next-Generation (NGS)/Massively parallel sequencing (MPS)

Other

Clinical Information

Test purpose:

Diagnosis

Clinical utility:

Establish or confirm diagnosis

View citations (1)

https://www.uab.edu/medicine/genetics/medical-genomics-laboratory/testing-services/nf1-legius-syndrome-and-rasopathies/nnp-ng

Target population:

Patients with clinical features suggestive of either NS, NSML, CFC, Legius syndrome or Noonan-like syndrome with no mutation previously found by comprehensive RNA-based NF1+/- SPRED1 testing. patients with a clinical diagnosis of any of these syndromes that previously tested negative in a subset of the genes included in this panel; … View more

Variant Interpretation:

What is the protocol for interpreting a variation as a VUS?
In order to further investigate a VUS, the laboratory will: 1. Review software predictions (SIFT, PolyPhen, etc) 2. Review internal database to compare against alterations seen in >10,000 alleles previously tested in laboratory 3. Offer free of charge family studies for any individuals that would provide useful information for interpretation

Are family members with defined clinical status recruited to assess significance of VUS without charge?
Yes.

Will the lab re-contact the ordering physician if variant interpretation changes?
Yes.

Recommended fields not provided:

Clinical validity, Is research allowed on the sample after clinical testing is complete?, Sample negative report, Sample positive report

Technical Information

Availability:

Tests performed
Entire test performed in-house

Analytical Validity:

Analytical sensitivity of next generation sequencing is typically validated using a minimum of 20 DNA samples. No false positives were detected during analysis. The average coverage is >2000x with >98.5% of the coding region ≥350x and 99.3% ≥200x, allowing detection of very low-level mosaicism, down to 3-5% variant allele fraction … View more

Proficiency testing (PT):

Is proficiency testing performed for this test?
Yes

Method used for proficiency testing:
Alternative Assessment

VUS:

Software used to interpret novel variations
Alamut, Google search, PolyPhen, SIFT, evolutionary consevation, grantham score, splicing prediction software, disorder specific databases as necessary

Laboratory's policy on reporting novel variations
The laboratory will issue an interim report summarizing what is currently known about the variant and familial studies will be offered. Upon completion of the familial studies, a final report will be provided with a conclusion of what is suspected for the alteration.

Recommended fields not provided:

Test Confirmation, Assay limitations, Description of internal test validation method, Citations for Analytical validity, PT Provider, Description of PT method, Major CAP category, CAP category, CAP test list

Regulatory Approval

FDA Review:

Category: Not Applicable

Additional Information

Reviews:

Genereviews

PubMed Clinical Queries

Clinical resources:

Molecular resources:

View MAP2K1 variations in ClinVar

View PTPN11 variations in ClinVar

RefSeqGene

Consumer resources:

Genetic Alliance

MedlinePlusGenetics (GHR)

NCATS Office of Rare Diseases Research (GARD)

MedlinePlus

IMPORTANT NOTE: NIH does not independently verify information submitted to GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.