Interpretive Handbook

Test 61488 :
PTEN Gene, Known Mutation

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Germline mutations in the PTEN gene are associated with a rare collection of clinical syndromes referred to as PTEN hamartoma tumor syndrome (PHTS). This includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome (PS) and Proteus-like syndrome (PLS). Although each of these syndromes has its own unique features, all 4 appear to be associated with multiple hamartomatous lesions, vascular lesions, and macrocephaly. Affected individuals may have an increased risk of cancer, including cancers of the breast, endometrium, thyroid, colon, and kidney. PHTS is an autosomal dominant disorder and penetrance is believed to be quite high.


CS is a multiple hamartoma syndrome associated with trichilemmomas, mucocutaneous papillomatous papules, and macrocephaly. Affected individuals are at an increased risk for breast, thyroid, and endometrial carcinoma.


BRRS is characterized by macrocephaly, intestinal hamartomas, lipomatosis, hemangiomatosis, and pigmented macules on the glans penis.


PS is associated with congenital malformations, overgrowth, macrocephaly, hyperostosis, connective tissue nevi, and epidermal nevi.


Proteus-like syndrome refers to individuals that have features of PS, but do not meet diagnostic criteria.


Note: This test is appropriate for predictive testing in families in which a point mutation or small insertion/deletion/duplication has been identified. SDEL / Single-Gene Large Deletion and Duplication Analysis is appropriate for predictive testing in families in which a large deletion or duplication (whole exon or multiexon) has been identified. If a familial mutation has not been previously identified, full analysis of the PTEN gene is more appropriate (see PTENS / PTEN Gene, Full Gene Analysis).

Useful For Suggests clinical disorders or settings where the test may be helpful

Confirming a diagnosis of PTEN hamartoma tumor syndrome, which includes Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, or Proteus-like syndrome


Screening of at-risk individuals when a mutations in the PTEN gene has been identified in an affected family member

Interpretation Provides information to assist in interpretation of the test results

All detected alterations are evaluated according to American College of Medical Genetics (ACMG) recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order PTENS / PTEN Gene, Full Gene Analysis.


Analysis is performed for the familial mutation provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with PTEN hamartoma tumor syndrome (Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, or Proteus-like syndrome).


We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.


A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med 2008 Apr;10(4):294-300

2. Eng C: PTEN Hamartoma Tumor Syndrome (PHTS). In GeneReviews (Internet). Edited by RA Pagon, TD Bird, CR Dolan, et al. University of Washington, Seattle, Updated 2011 Jul 21

3. Pilarski R, Stephens JA, Noss R, et al: Predicting PTEN mutations: an evaluation of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome clinical features. J Med Genet 2011 Aug;48(8):505-512

4. Zhou XP, Waite KA, Pilarski R, et al: 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 2003 Aug;73(2):404-411

5. Tan MH, Mester J, Peterson C, et al: A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands. Am J Hum Genet 2011 Jan;88:42-56