Tuberous Sclerosis Complex (TSC) NGS Panel

Test Information

Turnaround Time

5 weeks

CPT Code(s)

81406, 81407




  • TSC1
  • TSC2

Clinical Information

This panel includes the two genes that have been associated with tuberous sclerosis complex (TSC). This condition has an estimated prevalence of 1 in 6,000-10,000 individuals, and the clinical features associated with TSC1 versus TSC2 pathogenic variants are indistinguishable . Skin findings are one of the most consistent clinical features, and these can include the following: hypopigmented macules such as ash-leaf spots or confetti lesions, facial angiofibromas, shagreen patches, and ungual fibromas. Neurological findings typically have the most significant impact on health and development with tumors of the central nervous system being a major contributor to morbidity and mortality in TSC. Seizures are present in up to 80% of affected individuals, and brain imaging may reveal the presence of cortical tubers as well as subependymal nodules (SEN) or giant cell astrocytoma (SEGA). A majority of patients have intellectual disability to varying degrees, and autism spectrum disorders, ADHD, behavioral issues, and sleep problems may also occur. Additional signs include cardiac rhabdomyomas, retinal hamartomas, renal cysts, renal angiomyolipoma which is associated with the risk of malignancy, and lymphangioleiomyomatosis, particularly in adult women with TSC. Routine surveillance is recommended across multiple body systems to allow for early detection and potential intervention for some of these concerns. Tuberous sclerosis is considered to be an autosomal dominant disorder, but a majority of cases are due to de novo mutations or germline mosaicism. New mutations occur at a higher rate in TSC1 than TSC2. Significant variability in the degree of expression is a major feature of this condition, even within the same family. In general, pathogenic variants in TSC2 are associated with a more severe phenotype than pathogenic TSC1 alterations.


Molecular testing is useful to confirm the diagnosis and to identify the disease-causing mutations within a family to allow for carrier testing.


Next Generation Sequencing


The current design of the tuberous sclerosis panel covers the coding region for both genes and the flanking intronic sequences. This method allows for analysis of greater than 98% of the targeted sequence for the detection of nucleotide substitutions and small deletions and duplications. Large deletions and duplications will not be detected by this panel. Mutations and variants identified on the panel are confirmed with Sanger sequencing. All novel and apparently pathogenic changes are reported when found within the coding region as well as within 10 base pairs of each intron/exon boundary for each gene. Promoter and 3' untranslated sequences are not included in the current analysis. It should be noted that the current protocol is not specifically designed to detect copy number alterations and single exon deletions may require additional follow-up to determine whether or not they represent technical artifacts. We recommend further array-based testing to more accurately address the concerns of dosage alterations. The Cytogenetic Laboratory at GGC offers a high resolution microarray.

Specimen Requirements

The preferred sample type is 3-5 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. Saliva samples must be submitted in an approved saliva kit. Contact the lab to receive a saliva kit or to have one sent to your patient.

Transport Instructions

The specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.

Prenatal Testing Information

If the pathogenic mutation(s) are identified in an affected individual using this panel, prenatal diagnosis is available for future pregnancies. Sanger sequencing will be used for prenatal diagnosis when there is a known familial mutation. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.

Have Questions? Need Support?

Call our laboratory at 1-800-473-9411 or contact one of our Laboratory Genetic Counselors for assistance.
Robin Fletcher, MS, CGC
Falecia Thomas, MS, CGC

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