*If prior authorization is not submitted, test may be delayed.
Test Overview
All coding exons (plus 15 bp upstream and downstream of each coding exon) of the targeted gene(s) are captured, sequenced using NGS and aligned to the human reference genome. A minimum NGS coverage of 20X is achieved for all coding exons +/- 5 bp, and a minimum coverage of 10X an additional 10 bp from +/- 6 bp through +/- 15 bp. A minimum coverage of 10X is achieved for all clinically significant promoter regions. Regions which do not meet these coverage metrics are filled with targeted Sanger Sequencing. Variants in the targeted regions that are of potential clinical significance, based on the ACMG guidelines for interpretation of sequence variants (PMID: 25741868), will be reported. All reported variants of potential clinical significance not meeting the sequencing quality criteria will be confirmed by a different technology. Copy number variation is assessed by coverage depth within the targeted regions compared to a normalized reference file.
This test is used to detect the presence of PTEN mutations in patients with PTEN Hamartoma Tumor Syndrome (PHTS); the PHTS diagnosis includes Cowden Disease (CD)/Cowden Syndrome (CS), Bannayan-Riley-Ruvalcaba Syndrome (BRSS), Proteus Syndrome (PS), and Proteus-like syndromes. This test is also appropriate for patients exhibiting Macrocephaly/Autism Syndrome or VACTERL association with hydrocephalus, and for carrier testing in families with a known PTEN mutation. Approximately 10% of previously classified PTEN mutation-negative patients have nucleotide variants within the full-length promoter, and these mutations resulted in both a decrease in PTEN protein expression and loss of function (Teresi et al., AGHJ, V81, 756-767, 2007).
Interpretive report provided.
* Reference ranges may change over time. Please refer to the original patient report when evaluating results.
This analysis may not identify variants in the regulatory elements or deep intronic regions of the targeted gene(s) or other regions of the genome that are not included in this test. This assay may not detect small copy number variants (1-2 exons), or balanced inversion/translocations involving the targeted gene(s). Variant classification reflects the current state of scientific understanding at the time of test completion. As new scientific data becomes available, the interpretation and classification of variants identified in this assay may change. Test interpretation may be impacted by the presence of a hematologic malignancy or an allogenic bone marrow transplant.
Test Details
21 - 28 days
- Cowden Syndrome (CS)
- Bannayan-Riley-Ruvalcaba Syndrome (BRRS)
- Proteus and Proteus-like Syndrome
- Macrocephaly / Autism Syndrome
- PTEN Promoter Sequencing
- Cowden Disease (CD)
- Autism / Intellectual Disability
Specimen Requirements
Collect blood specimen in a EDTA lavender top tube. Send it within 24 hours if stored at room temperature or within 5 days if stored refrigerated.
Fill out a MLabs Molecular test requisition (or place an e-order if applicable):
https://mlabs.umich.edu/media/166
Fill out a Clinical History Form for Insurance Prior Authorization (include all required documentation indicated at the bottom of this form):
https://mlabs.umich.edu/sites/default/files/2020-08/file/mlab11618clini…
Fill out a UMHS Request and Consent for Genetic Testing form:
https://mlabs.umich.edu/sites/default/files/2023-04/file/germline-conse…
Michigan State law requires the ordering provider to obtaining informed consent from the patient prior to prognostic or predictive genetic testing. Contact a MLabs Client Services Center at 800-862-7284 to request paper copies or to setup a client account.
Saliva kit (Oragene OGD-510), follow collection instructions.
2-36°C for saliva
Additional Information
Most insurance carriers require prior authorization for genetic testing. Testing will not begin until insurance prior authorization is received by the laboratory or it is confirmed that prior authorization is not required. The ordering health care provider can obtain the prior authorization or request the laboratory to submit it. To obtain BCN prior authorization call Joint Venture Hospital Laboratories (JVHL) at 800-445-4979; for all other insurances, contact the plan directly. By ordering this test the clinician acknowledges that informed consent, https://mlabs.umich.edu/sites/default/files/2023-04/file/germline-conse…, has been obtained from the patient as required by applicable state or federal laws and the ordering clinician has authorization from the patient permitting MLabs to report the test results to the ordering clinician. Test includes medical geneticist interpretation of results billed as a separate additional charge. This test is not available without interpretation.