Known Mutation Testing (KT2)                                                    


Mendelian Inheritance in Man number: 162200

Click here for Gene Reviews Clinical Summary.

Neurofibromatosis type 1 is a completely penetrant, autosomal dominant disorder with a frequency of 1/3500 births in all ethnic populations. NF1 is a progressive disorder, characterized by multiple café-au-lait spots, neurofibromas, and Lisch nodules, although additional features may develop.  NF1 is notorious for its variable expression. About 50% of cases are due to new dominant mutations, where neither parent has signs of the disorder. An affected individual has a 50% risk of transmitting NF1 to each offspring, although the degree of severity can differ from person to person, even within the same family. 


  • Predictive testing for individuals at risk of inheriting an already known NF1 mutation
  • Individuals who want to prepare for prenatal / pre-implantation diagnosis
  • Targeted testing of all relevant relatives of a proband in whom a novel missense variant was identified.


We offer a targeted detection of a previously characterized NF1 mutation within the family. Depending on the mutation identified previously in the family, targeted testing can involve FISH analysis, direct sequencing of a specific region or copy number analysis by MLPA.

KT2 is provided free of charge to all relevant relatives of a proband in whom a novel missense alteration was found that needs further clarification to come to a final conclusion.  As the final conclusion on the pathogenicity of a missense alteration relies on accurate phenotypic data, the testing in relevant relatives is provided free of charge only if a phenotypic checklist is filled out by a healthcare professional that made the clinical assessment of the relatives.  The correct interpretation of the results also relies on the correct disclosure of the biological relationships. 


We require 1 milliliter of whole blood. Blood samples must be collected in EDTA (purple topped) tubes. 



If specimen is from clinics within UAB or Kirklin Clinic, please call 934-7107 for pick-up. If specimens are being sent from some other location, please ship via UPS or Federal Express.

1. Be sure that the shipping air bill is marked “Priority”, either Domestic or International.
2. Specimens must be packaged to prevent breakage and absorbent material must be included in the package to absorb liquids in the event that breakage occurs.  Also, the package must be shipped in double watertight containers (e.g. a specimen pouch + the shipping companies Diagnostic Envelope). You can use our collection kits, which we will send to physicians directly upon request.


15 working days


Please find the most up to date prices and CPT codes for our testing services under the "Prices" tab of this website.


NF1 Test Requisition including the phenotypic data form

Form for Customs (International shipment)

Note: Detailed and accurate completion of this document is necessary for reporting purposes. The Medical Genomics Laboratory issues its clinical reports based on the demographic data provided by the referring institution on the lab requisition form. It is the responsibility of the referring institution to provide accurate information. If an amended report is necessary due to inaccurate or illegible documentation, additional reports will be drafted with charge.

Requests for Molecular Genetic testing for NF1 will not be accepted for the following reasons:

  • No label (patient’s full name and date of collection) on the specimens
  • No referring physician’s or genetic counselor’s names and addresses
  • No billing information if this is a fee for service test
  • No informed consent
  • No phenotypic checklist: we offer free of charge targeted testing to all relevant relatives of a proband in whom a novel missense variant was identified. Testing of these relatives may allow us to make a final conclusion on the pathogenicity of the novel missense variant and allow us to provide better counseling now and in the future. Free of charge targeted testing will only be provided if the necessary phenotypic information on the proband and relatives filled out by a healthcare professional accompanies the samples. If no phenotypic information is provided, we will charge the institution for the test.

For more information, test requisition forms, or sample collection and mailing kits, please call: 205-934-5562.


Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A, Viskochil D. (1997) The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA. Jul 2; 278(1): 51-7. Review. (pubmed)

Huson, SM; Hughes, RAC: The Neurofibromatoses: a Pathogenetic and Clinical Overview. London: Chapman & Hall Medical, 1994. (pubmed)

Maertens O, De Schepper S, Vandesompele J, Brems H, Heyns I, Janssens S, Speleman F, Legius E, Messiaen L (2007) Molecular dissection of isolated disease features in mosaic neurofibromatosis type 1. Am J Hum Genet 81(2):243-251. (pubmed)

Messiaen LM, Callens T, Mortier G, Beysen D, Vandenbroucke I, Van Roy N, Speleman F, De Paepe A (2000) Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frecuqency of unusual splicing defects. Hum Mutat.15(6):541-55. (pubmed)

Messiaen L and Wimmer K (2005) Pitfalls of automated comparative sequence analysis as a single platform for routine clinical testing for NF1. J. Med. Genet. 42(5): e25. (pubmed)

Messiaen LM and Wimmer K (2008) NF1 Mutational Spectrum, in Kaufmann D (ed): Neurofibromatoses. Monogr Hum Genet. Basel, Karger, Vol 16:63-77 (pubmed)

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 (2007) 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 80(1):140-51. (pubmed)

Wimmer K,  Roca X, Beiglbock H, Callens T, Etzler J, Rao A, Krainer A, Fonatsch C, Messiaen L (2007) Extensive in silico analysis of NF1 splicing defects uncovers determinants for splicing outcome upon 5’ splice-site disruption. Hum Mutat. 28(6): 599-612. (pubmed)