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Test Code TSCP Tuberous Sclerosis Gene Panel, Varies


Ordering Guidance


Targeted testing (also called site-specific or known variant testing) is available for variants identified in this gene. See FMTT / Familial Variant, Targeted Testing, Varies.

 

Customization of this panel and single gene analysis for any gene present on this panel are available. See CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.



Additional Testing Requirements


All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen as this must be a different order number than the prenatal specimen.



Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Specimen Required


Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115)

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory.

Specimen Stability Information: Ambient (preferred)/Refrigerated (<24 hours)

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Blood spot

Supplies: Card-Blood Spot Collection (Filtration Paper) (T493)

Container/Tube:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper or blood spot collection card (T493)

Specimen Volume: 5 Blood spots

Collection Instructions:

1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect Dried Blood Spot Samples.

2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.

3. Do not expose specimen to heat or direct sunlight.

4. Do not stack wet specimens.

5. Keep specimen dry.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Additional Information:

1. Due to lower concentration of DNA yielded from blood spot, it is possible that additional specimen may be required to complete testing.

2. For collection instructions, see Blood Spot Collection Instructions

3. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)

4. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800)

 

Specimen Type: Saliva

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Swab Collection Kit (T786)

Specimen Volume: 1 Swab

Collection Instructions: Collect and send specimen per kit instructions.

Additional Information: Due to lower concentration of DNA yielded from saliva, it is possible that additional specimen may be required to complete testing.

Specimen Stability Information: Ambient 30 days

 

Prenatal Specimens

Due to its complexity, consultation with the laboratory is required for all prenatal testing; call 800-533-1710 to speak to a genetic counselor.

 

Specimen Type: Amniotic fluid

Container/Tube: Amniotic fluid container

Specimen Volume: 20 mL

Specimen Stability Information: Refrigerated (preferred)/Ambient

Additional information:

1. A separate culture charge will be assessed under CULAF / Culture for Genetic Testing, Amniotic Fluid.

2. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

 

Specimen Type: Chorionic villi

Container/Tube: 15-mL tube containing 15 mL of transport media

Specimen Volume: 20 mg

Specimen Stability Information: Refrigerated

Additional Information:

1. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing.

2. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

 

Acceptable:

Specimen Type: Confluent cultured cells

Container/Tube: T-25 flask

Specimen Volume: 2 flasks

Collection Instructions: Submit confluent cultured cells from another laboratory.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Additional Information: All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.


Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

2. Molecular Genetics: Neurology Patient Information

3. If not ordering electronically, complete, print, and send one of the following with the specimen:

-Neurology Specialty Testing Client Test Request (T732)

-Cardiovascular Test Request Form (T724)

Secondary ID

616537

Useful For

Establishing a molecular diagnosis in individuals with features of tuberous sclerosis complex (TSC).

 

Identifying pathogenic variants within the TSC1 and TSC2 genes known to be associated with TSC, allowing for predictive testing of at-risk family members.

 

Prenatal diagnosis in a fetus with ultrasound findings of TSC (eg, cardiac rhabdomyomas)

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
MATCC Maternal Cell Contamination, B Yes No
CULAF Amniotic Fluid Culture/Genetic Test Yes No
CULFB Fibroblast Culture for Genetic Test Yes No

Testing Algorithm

For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

 

For prenatal specimens only:

If an amniotic fluid specimen or nonconfluent cultures are received, amniotic fluid culture/genetic test will be added at an additional charge.

For any prenatal specimen that is received, maternal cell contamination testing will be performed at an additional charge.

 

For more information see Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm

Method Name

Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.

Reporting Name

Tuberous Sclerosis Gene Panel

Specimen Type

Varies

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Reject Due To

All specimens will be evaluated by Mayo Clinic Laboratories for test suitability.

Clinical Information

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder associated with pathogenic variants in the TSC1 and TSC2 genes. TSC involves multiple organ systems including the skin (angiofibroma, hypomelanotic macule, Shagreen patch), brain (cortical tuber, subependymal nodule and giant cell astrocytoma, seizures including infantile spasms), kidneys (angiomyolipoma), heart (rhabdomyoma), eye (multiple retinal nodular hamartomas) and lungs (lymphangioleiomyomatosis). TSC may also be associated with autism, cognitive impairment, and psychiatric difficulties. Central nervous system tumors are the leading cause of morbidity and mortality.

 

Approximately one-third of individuals with TSC have an affected parent, and two-thirds occur as a result of a de novo disease-causing variant. Although penetrance is complete, TSC is associated with significant inter- and intrafamilial variability in phenotype.

Reference Values

An interpretive report will be provided.

Interpretation

All detected variants are evaluated according to American College of Medical Genetics and Genomics (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

Clinical Correlations:
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals.

 

To discuss the availability of additional testing options or for assistance in the interpretation of these results, contact Mayo Clinic Laboratories genetic counselors at 800-533-1710.

 

Technical Limitations:
Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered.

 

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.

 

This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Deletions-insertions (delins) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller delins.

 

Deletion/Duplication Analysis:

This analysis targets single and multi-exon deletions/duplications; however, in some instances single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.

 

This test is not designed to detect low levels of mosaicism or to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.

 

Genes may be added or removed based on updated clinical relevance. For detailed information regarding gene specific performance and technical limitations, see Method Description or contact a laboratory Genetic Counselor.

 

If the patient has had an allogeneic hematopoietic stem cell transplant or a recent heterologous blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.

 

Reclassification of Variants:
 At this time, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages health care providers to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time. Due to broadening genetic knowledge, it is possible that the laboratory may discover new information of relevance to the patient. Should that occur the laboratory may issue an amended report.

 

Variant Evaluation:
Evaluation and categorization of variants are performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline.(1) Other gene-specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported.

 

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgement.

 

Rarely, incidental findings or secondary findings may implicate another predisposition or presence of active disease. These findings  will be carefully reviewed to determine whether or not they will be reported.

Clinical Reference

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424. doi: 10.1038/gim.2015.30

2. Northrup H, Aronow M, Bebin E, et al: Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations. Pediatr Neurol. 2021 Oct;123:50-66. doi: 10.1016/j.pediatrneurol.2021.07.011

Method Description

Next-generation sequencing (NGS) and/or Sanger sequencing is performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletion/insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp, and insertions up to 47 bp. NGS and/or a polymerase chain reaction (PCR)-based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed.

 

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences.(Unpublished Mayo method)

 

Genes analyzed: TSC1, TSC2

Day(s) Performed

Varies

Report Available

28 to 42 days

Specimen Retention Time

Whole blood: 2 weeks (if available); Extracted DNA: 3 months; Blood spots, saliva, cultured fibroblasts, skin biopsy, cord blood, amniotic fluid, cultured amniocytes, chorionic villi, cultured chorionic villi: 1 month

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

81406

81407

81265-Maternal cell contamination (if appropriate) 88233-Tissue culture, skin, solid tissue biopsy (if appropriate) 88235-Amniotic Fluid culture (if appropriate) 88240-Cryopreservation (if appropriate)

81479 (if appropriate for government payers)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
TSCP Tuberous Sclerosis Gene Panel 34650-2

 

Result ID Test Result Name Result LOINC Value
616538 Test Description 62364-5
616539 Specimen 31208-2
616540 Source 31208-2
616541 Result Summary 50397-9
616542 Result 82939-0
616543 Interpretation 69047-9
616544 Resources In Process
616545 Additional Information 48767-8
616546 Method 85069-3
616547 Genes Analyzed 48018-6
616548 Disclaimer 62364-5
616549 Released By 18771-6