Tuberous Sclerosis Complex NGS panel - Clinical Genetic Test - GTR

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Tuberous Sclerosis Complex NGS panel

Clinical Genetic Test

offered by

UAB Medical Genomics Laboratory

View lab's test page

GTR Test Accession: GTR000551658.6

INHERITED DISEASEINHERITED DISEASE SUSCEPTIBILITYCANCER ... View more

Last updated in GTR: 2023-06-07

Last annual review date for the lab: 2023-06-07 Past due

At a Glance

Test purpose:

Diagnosis; Mutation Confirmation; Risk Assessment

Conditions (2):

Tuberous sclerosis 1; Tuberous sclerosis 2

Genes (2):

TSC1 (9q34.13); TSC2 (16p13.3)

Methods (2):

Molecular Genetics - Deletion/duplication analysis: Multiplex Ligation-dependent Probe Amplification (MLPA); ...

Target population:

Patients with one or more features associated with TSC with …

Clinical validity:

Not provided

Clinical utility:

Establish or confirm diagnosis

Ordering Information

Offered by:

UAB Medical Genomics Laboratory
View lab's website
View lab's test page

Test short name:

TSCP-NG

Specimen Source:

Fresh tissue
Frozen tissue
Isolated DNA
Peripheral (whole) blood
Saliva
Skin

Who can order:

Genetic Counselor
Health Care Provider
Licensed Physician
Nurse Practitioner
Physician Assistant

Test Order Code:

TSCP-NG
View other test codes

CPT codes:

**AMA CPT codes notice

Lab contact:

Brandon Shaw, MS, CGC, Certified Genetic counselor, CGC, Genetic Counselor
brandonshaw@uabmc.edu
205-934-1520

Contact Policy:

Pre-test email/phone consultation regarding genetic test results and interpretation is provided to patients/families.

How to Order:

Additional information regarding the specific details needed for test submission can be found on our website
Order URL

Test service:

Clinical Testing/Confirmation of Mutations Identified Previously
Custom Deletion/Duplication Testing
Result interpretation

Test development:

Test developed by laboratory but exempt from FDA oversight (eg. NYS CLEP approved, offered within a hospital or clinic)

Informed consent required:

Based on applicable state law

Test strategy:

The Tuberous Sclerosis Complex panel by NGS involves the simultaneous sequencing of 2 genes: TSC1 and TSC2. The average coverage is >2000x with >99% of the coding region covered at ≥350x and >99.4% ≥200x. The minimum coverage for any additional areas is >30x. This allows for detection of very low … The Tuberous Sclerosis Complex panel by NGS involves the simultaneous sequencing of 2 genes: TSC1 and TSC2. The average coverage is >2000x with >99% of the coding region covered at ≥350x and >99.4% ≥200x. The minimum coverage for any additional areas is >30x. This allows for detection of very low level mosiacism by sequencing (as low as 8% of the alleles in all regions analyzed by NGS; >99% of the coding region does provide deeper coverage with the ability to identify substitution variants as low as 3% of the alleles). Variant and copy number calls are made using a unique bioinformatics pipeline detecting all types of variants including single nucleotide substitutions, indels and frameshifts caused by deletion or duplication up to 112bp. Deletion/duplication analysis for TSC1 and TSC2 is included in this test, as such variants are a part of the variant spectrum for these conditions. Validation of the full panel included, besides substitutions (missense, nonsense, splice variants), the most challenging variants such as insertions/deletions/duplications of 1-112bp and one-to-multiple exon deletions/duplications. The analytical sensitivity of our NGS testing approach was 100% for substitutions as well as insertion/deletions up to 112bp. This panel has not yet been validated to identify deletions/duplications >112bp and <1 exon, but such variants have not yet been found in the UAB cohort, and therefore are likely very rare. The panel has been validated for the detection of germline (heterozygous) single-exon deletions/duplications as well as multi-exon deletions/duplications, however mosaic single-exon deletion/duplications validation is still pending. Relevant family members of a proband with any (novel or previously identified) variant of unknown significance are offered free of charge targeted analysis as long as accurate phenotypic data are provided by a health care professional to enhance the interpretation. There is no limitation to the number of relatives that can be tested free of charge. Analysis can be performed on fresh or frozen affected tissue via next-generation sequencing. View more

Pre-test genetic counseling required:

Decline to answer

Post-test genetic counseling required:

Decline to answer

Conditions

Total conditions: 2

Condition/Phenotype	Identifier

Test Targets

Genes

Total genes: 2

Gene	Associated Condition	Germline or Somatic	Allele (Lab-provided)	Variant in NCBI

Methodology

Total methods: 2

Method Category

Test method

Instrument *

Deletion/duplication analysis

Multiplex Ligation-dependent Probe Amplification (MLPA)

Sequence analysis of the entire coding region

Next-Generation (NGS)/Massively parallel sequencing (MPS)

* Instrument: Not provided

Clinical Information

Test purpose:

Diagnosis; Mutation Confirmation; Risk Assessment

Clinical utility:

Establish or confirm diagnosis

View citations (1)

https://www.uab.edu/medicine/genetics/medical-genomics-laboratory/testing-services/tuberous-sclerosis

Target population:

Patients with one or more features associated with TSC with or without a family history of TSC.

Variant Interpretation:

What is the protocol for interpreting a variation as a VUS?
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?
Yes.

Will the lab re-contact the ordering physician if variant interpretation changes?
Yes.

Recommended fields not provided:

Clinical validity, Is research allowed on the sample after clinical testing is complete?, Sample negative report, Sample positive report

Technical Information

Availability:

Tests performed
Entire test performed in-house

Analytical Validity:

Analytical sensitivity of next generation sequencing is typically validated using a minimum of 20 DNA samples. No false positives were detected during analysis. The average coverage is >2000x with >99% of the coding region covered at ≥350x and >99.4% ≥200x. The minimum coverage for any additional areas is >30x. This … View more

View citations (2)

Northrup H, Koenig MK, Pearson DA, Au KS. Tuberous Sclerosis Complex. 1999 Jul 13 [updated 2024 Aug 01]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301399.
https://www.ncbi.nlm.nih.gov/books/NBK1220

Proficiency testing (PT):

Is proficiency testing performed for this test?
Yes

Method used for proficiency testing:
Intra-Laboratory

VUS:

Software used to interpret novel variations
Alamut, Google search, PolyPhen, SIFT, evolutionary consevation, grantham score, splicing prediction software, disorder specific databases as necessary

Laboratory's policy on reporting novel variations
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:

Test Confirmation, Assay limitations, Description of internal test validation method, PT Provider, Description of PT method, Major CAP category, CAP category, CAP test list

Regulatory Approval

FDA Review:

Category: FDA exercises enforcement discretion

Additional Information

Reviews:

Genereviews

PubMed Clinical Queries

Clinical resources:

Molecular resources:

View TSC1 variations in ClinVar

RefSeqGene

Coriell Institute for Medical Research

Practice guidelines:

Orphanet, 2007

Consumer resources:

MalaCards

MedlinePlusGenetics (GHR)

MedlinePlus

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.