RNA-based NF1 and SPRED1 Comprehensive Testing
GTR Test Accession: Help GTR000568134.4
CAP
INHERITED DISEASEDYSMORPHOLOGYINHERITED DISEASE SUSCEPTIBILITY ... View more
Last updated in GTR: 2023-06-07
Last annual review date for the lab: 2023-06-07 Past due LinkOut
At a Glance
Diagnosis; Mutation Confirmation; Pre-symptomatic; ...
Neurofibromatosis, type 1; Legius syndrome
Genes (2): Help
NF1 (17q11.2), SPRED1 (15q14)
Molecular Genetics - Deletion/duplication analysis: Multiplex Ligation-dependent Probe Amplification (MLPA); ...
Patients who need the most sensitive and specific test with …
Not provided
Not provided
Ordering Information
Offered by: Help
Test short name: Help
NFSP-R
Specimen Source: Help
Who can order: Help
  • Genetic Counselor
  • Health Care Provider
  • Licensed Physician
  • Nurse Practitioner
  • Physician Assistant
CPT codes: Help
**AMA CPT codes notice
Lab contact: Help
Bryce Brown, MS, CGC, Certified Genetic counselor, CGC, Genetic Counselor
ebfincher@uabmc.edu
205-934-5525
Brandon Shaw, MS, CGC, Certified Genetic counselor, CGC, Genetic Counselor
brandonshaw@uabmc.edu
205-934-1520
Contact Policy: Help
Pre-test email/phone consultation regarding genetic test results and interpretation is provided to patients/families.
How to Order: Help
Additional information regarding the specific details needed for test submission can be found on our website
Order URL
Test development: Help
Test developed by laboratory (no manufacturer test name)
Informed consent required: Help
Based on applicable state law
Test strategy: Help
The RNA-based NF1 and DNA-based SPRED1 testing on blood requires a fresh EDTA blood sample, to arrive in the lab <60-70 hours after blood draw. DNA is extracted and in addition, a short term phytohemagglutinin-stimulated lymphocyte culture is initiated and used as starting material to extract RNA. The complete NF1 … View more
View citations (10)
  • Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects. Messiaen LM, et al. Hum Mutat. 2000;15(6):541-55. doi:10.1002/1098-1004(200006)15:6<541::AID-HUMU6>3.0.CO;2-N. PMID: 10862084.
  • Pitfalls of automated comparative sequence analysis as a single platform for routine clinical testing for NF1. Messiaen LM, et al. J Med Genet. 2005;42(5):e25. PMID: 15863657.
  • Spectrum of single- and multiexon NF1 copy number changes in a cohort of 1,100 unselected NF1 patients. Wimmer K, et al. Genes Chromosomes Cancer. 2006;45(3):265-76. doi:10.1002/gcc.20289. PMID: 16283621.
  • Upadhyaya M, Huson SM, Davies M, Thomas N, Chuzhanova N, Giovannini S, Evans DG, Howard E, Kerr B, Griffiths S, Consoli C, Side L, Adams D, Pierpont M, Hachen R, Barnicoat A, Li H, Wallace P, Van Biervliet JP, Stevenson D, Viskochil D, Baralle D, Haan E, Riccardi V, Turnpenny P, Lazaro C, Messiaen L. An absence of cutaneous neurofibromas associated with a 3-bp inframe deletion in exon 17 of the NF1 gene (c.2970-2972 delAAT): evidence of a clinically significant NF1 genotype-phenotype correlation. Am J Hum Genet. 2007;80(1):140-51. doi:10.1086/510781. Epub 2006 Dec 08. PMID: 17160901.
  • Extensive in silico analysis of NF1 splicing defects uncovers determinants for splicing outcome upon 5' splice-site disruption. Wimmer K, et al. Hum Mutat. 2007;28(6):599-612. doi:10.1002/humu.20493. PMID: 17311297.
  • Maertens O, De Schepper S, Vandesompele J, Brems H, Heyns I, Janssens S, Speleman F, Legius E, Messiaen L. Molecular dissection of isolated disease features in mosaic neurofibromatosis type 1. Am J Hum Genet. 2007;81(2):243-51. doi:10.1086/519562. Epub 2007 Jun 20. PMID: 17668375.
  • Mosaic type-1 NF1 microdeletions as a cause of both generalized and segmental neurofibromatosis type-1 (NF1). Messiaen L, et al. Hum Mutat. 2011;32(2):213-9. doi:10.1002/humu.21418. PMID: 21280148.
  • The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. Gutmann DH, et al. JAMA. 1997;278(1):51-7. PMID: 9207339.
  • Huson, SM; Hughes, RAC: The Neurofibromatoses: a Pathogenetic and Clinical Overview. London: Chapman & Hall Medical, 1994
  • Messiaen LM and Wimmer K (2008) NF1 Mutational Spectrum, in Kaufmann D (ed): Neurofibromatoses. Monogr Hum Genet. Basel, Karger, Vol 16:63-77
Pre-test genetic counseling required: Help
Decline to answer
Post-test genetic counseling required: Help
Decline to answer
Recommended fields not provided:
Conditions Help
Total conditions: 2
Condition/Phenotype Identifier
Test Targets
Genes Help
Total genes: 2
Gene Associated Condition Germline or Somatic Allele (Lab-provided) Variant in NCBI
Methodology
Total methods: 3
Method Category Help
Test method Help
Instrument
Deletion/duplication analysis
Multiplex Ligation-dependent Probe Amplification (MLPA)
Sequence analysis of the entire coding region
Alternative splicing detection
Applied Biosystems 3730 capillary sequencing instrument
Sequence analysis of the entire coding region
Bi-directional Sanger Sequence Analysis
Applied Biosystems 3730 capillary sequencing instrument
Clinical Information
Test purpose: Help
Diagnosis; Mutation Confirmation; Pre-symptomatic; Risk Assessment
Target population: Help
Patients who need the most sensitive and specific test with the fastest turnaround time.
Variant Interpretation:
What is the protocol for interpreting a variation as a VUS? Help
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? Help
Yes. Free of charge testing is provided to necessary family members as long as appropriate clinical information is submitted with the blood specimen.

Will the lab re-contact the ordering physician if variant interpretation changes? Help
Yes.
Research:
Is research allowed on the sample after clinical testing is complete? Help
Yes
Recommended fields not provided:
Technical Information
Test Procedure: Help
The RNA-based NF1 and DNA-based SPRED1 testing on blood requires a fresh EDTA blood sample, to arrive in the lab <60-70 hours after blood draw. DNA is extracted and in addition, a short term phytohemagglutinin-stimulated lymphocyte culture is initiated and used as starting material to extract RNA. The complete NF1 … View more
Test Platform:
None/not applicable
Availability: Help
Tests performed
Entire test performed in-house
Analytical Validity: Help
The complete NF1 coding region is analyzed by a cascade of complementary mutation detection techniques, including RT-PCR, direct sequencing, microsatellite marker analysis, copy number analysis by MLPA, enabling us to identify the mutation in ~95% of non-founder patients fulfilling the NIH diagnostic criteria
View citations (4)
  • Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects. Messiaen LM, et al. Hum Mutat. 2000;15(6):541-55. doi:10.1002/1098-1004(200006)15:6<541::AID-HUMU6>3.0.CO;2-N. PMID: 10862084.
  • Pitfalls of automated comparative sequence analysis as a single platform for routine clinical testing for NF1. Messiaen LM, et al. J Med Genet. 2005;42(5):e25. PMID: 15863657.
  • Extensive in silico analysis of NF1 splicing defects uncovers determinants for splicing outcome upon 5' splice-site disruption. Wimmer K, et al. Hum Mutat. 2007;28(6):599-612. doi:10.1002/humu.20493. PMID: 17311297.
  • Messiaen LM and Wimmer K (2008) NF1 Mutational Spectrum, in Kaufmann D (ed): Neurofibromatoses. Monogr Hum Genet. Basel, Karger, Vol 16:63-77
Proficiency testing (PT):
Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Inter-Laboratory

PT Provider: Help
American College of Medical Genetics / College of American Pathologists, ACMG/CAP
VUS:
Software used to interpret novel variations Help
Alamut, Google search, PolyPhen, SIFT, evolutionary conservation, grantham score, splicing prediction software, disorder specific databases as necessary

Laboratory's policy on reporting novel variations Help
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:
Regulatory Approval
FDA Review: Help
Category: FDA exercises enforcement discretion
Additional Information

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.