Known Mutation Testing (KT2)


Mendelian Inheritance in Man number: *601728 (PTEN gene); 158350 (Cowden syndrome, CS); 153480 (Bannayan-Riley-Ruvalcaba syndrome, BRRS); 176920 (Proteus syndrome, PS); 605309 (Macrocephaly/Autism syndrome)

Click here for Gene Reviews Clinical Summary.

Please see PTEN1 description for detailed clinical information


  • Identification of pre-symptomatic carriers of a PTEN-associated mutation among family members of patients.
  • Individuals who want to prepare for prenatal / pre-implantation diagnosis


We offer a targeted detection of a previously characterized PTEN mutation within the family. Depending on the mutation identified previously in the family, targeted testing can involve 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 934-5562 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.


10 working days


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



PTEN Test Requisition including the phenotypic data form

Form for customs (International shipment)

Note: Requests for Molecular Genetic testing for PTEN 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
  • No informed consent
  • No phenotypic checklist
  • 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.



Barker K, Martinez A, Wang R, Bevan S, Murday V, Shipley J, Houlston R, Harper J (2001)  PTEN mutations are uncommon in Proteus syndrome  J Med Genet. 38: 480-1 (PubMed)

Buxbaum JD, Cai G, Chaste P, Nygren G, Goldsmith J, Reiehert J, et al. (2007) Mutation Screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly. Am J Med Genet. 144B:484-91. (PubMed)

Butler MG, Dasouki MJ, Zhou XP, Talebizadeh X, Brown M, Takahashi TN, et al. (2005) Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumor suppressor gene mutations. J Med Genet. 42:318-21. (PubMed)

Cohen MM Jr. (2005) Proteus syndrome: An update. Am J Med Genet. 137C:38-52. (PubMed)

Eng C. (2003) PTEN: one gene, many syndromes. Hum Mutat. 22(3):183-98. (PubMed)

Eng C, Thiele H, Zhou XP, Gorlin RJ, Hennekam RC, Winter RM  (2001)  PTEN mutations and proteus syndrome.  Lancet. 358: 210-1 (PubMed)

Goffin A, Hoefsloot LH, Bosgoed E, Swillen A, Fryns JP. (2001) PTEN Mutation in a Family With Cowden Syndrome and Autism.  Am J Med Genet 105(6):521-24. (PubMed)

Herman GE, Butter E, Enrile B, Matthew P, Prior TW, Sommer A. (2007) Increasing knowledge of PTEN germline mutations: two additional patients with autism and macrocephaly. Am J Med Genet. 143A:589-93. (PubMed)

Pezzolesi MG, Zbuk KM, Waite KA, Eng C (2007)  Comparative genomic and functional analyses reveal a novel cis-acting PTEN regulatory element as a highly conserved functional E-box motif deleted in Cowden syndrome  Hum Mol Genet. 16: 1058-71 (PubMed)

Smith JM, Kirk EP, Theodosopoulos G, Marshall GM, Walker J, Rogers M, Field M, Brereton JJ, Marsh DJ (2002) Germline mutation of the tumour suppressor PTEN in Proteus syndrome  J Med Genet. 39: 937-40 (PubMed)

Zhou XP, Waite KA, Pilarski R, Hampel H, Fernandez MJ, Bos C, Dasouki M, Feldman GL, Greenberg LA, Ivanovich J, Matloff E, Patterson A, Pierpont ME, Russo D, Nassif NT, Eng C (2003) Germline PTEN promoter mutations and deletions in Cowden/Bannayan-Riley-Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway.  Am J Hum Genet. 73: 404-11 (PubMed)

Zhou XP, Marsh DJ, Hampel H, Mulliken JB, Gimm O, Eng C (2000)  Germline and germline mosaic PTEN mutations associated with a Proteus-like syndrome of hemihypertrophy, lower limb asymmetry, arteriovenous malformations and lipomatosis  Hum Mol Genet. 9: 765-8 (PubMed)