Tuberous Sclerosis Complex Panel (TSC1, TSC2)

This test is used to identify individuals with autosomal dominant tuberous sclerosis complex (TSC). It detects single-nucleotide variants, deletions, and duplications in the TSC1 and TSC2 genes.

If a familial mutation has been detected by sequencing or deletion/duplication studies, the Hereditary Cancer Single Site(s) test (test code 93945) may be considered. Official test results of the family member must be available for laboratory review.

For more information, please visit our website QuestHereditaryCancer.com. To discuss a family history with a Quest Diagnostics genomic science specialist, please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463).

Testing may be indicated for individuals with a suspected diagnosis of TSC but not enough features to confirm a clinical diagnosis. A clinical diagnosis is confirmed for individuals with at least 1 major clinical feature or at least 2 minor features¹:

Major features

• Angiofibromas (≥3) or fibrous cephalic plaque
• Cardiac rhabdomyoma
• Cortical dysplasias, including tubers and cerebral white matter migration lines
• Hypomelanotic macules (3 to >5 mm in diameter)
• Lymphangioleiomyomatosis (LAM)
• Multiple retinal nodular hamartomas
• Renal angiomyolipoma
• Shagreen patch
• Subependymal giant cell astrocytoma (SEGA)
• Subependymal nodules (SENs)
• Ungual fibromas (≥2)

Minor features

• "Confetti" skin lesions (numerous 1- to 3-mm hypopigmented macules scattered over regions of the body such as the arms and legs)
• Dental enamel pits (>3)
• Intraoral fibromas (≥2)
• Multiple renal cysts
• Nonrenal hamartomas
• Retinal achromic patch

Informed consent is required, and genetic counseling is recommended. Whenever possible, consider testing the person in the family with the youngest age at the time of diagnosis related to TSC.

For more information or to discuss a family history with a Quest genomic science specialist, please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463).

The right time depends on the individual. An individual’s current medical status, personal experience with TSC, treatment or screening plan, and general readiness for genetic information all influence the decision to be tested. Having an open dialogue with individuals about these topics can assist with shared decision-making. Additionally, consider referring individuals to a clinical genomic science specialist for a thorough review of the individual’s family history and discussion of testing options.

Find a local genomic science specialist by visiting FindAGeneticCounselor.com. 

For most tests, results will be completed 14 to 21 days after receipt of the sample in the laboratory and completion of preauthorization. For tests with 12 or more genes, the turnaround time is 21 to 30 days.

Please note an additional 7 to 10 days for confirmation of copy number variants (CNVs) by an orthogonal method may be needed. Turnaround time may vary based on delays caused by incomplete orders or insurance authorizations.

Individuals with a positive result have a pathogenic or likely pathogenic variant detected in the TSC1 or TSC2 gene and a diagnosis of autosomal dominant TSC. A positive result does not mean that an individual has all the clinical features of TSC or will definitely develop them in the future. Specific risk information will be provided in the result report, and you can visit the website QuestHereditaryCancer.com for more information. 

Additionally, Tuberous Sclerosis Complex International has published clinical consensus guidelines for surveillance and management of individuals with TSC.²

A negative result means that a pathogenic or likely pathogenic variant was not detected in the TSC1 or TSC2 genes. For more information regarding specific genetic variants analyzed in this assay, please refer to the methods and limitations section of the genetic testing report. Clinical diagnostic criteria are available if an individual is still suspected of having a diagnosis of TSC in the context of a negative genetic testing result.^1,2

A VUS result means that the variant has not been previously described in the literature or that the clinical significance is unclear based upon currently available evidence. Medical management decisions should be based on personal and family history. Family studies may inform the clinical significance of this variant.

The classification and interpretation of the variant(s) identified reflect the current state of Quest’s understanding at the time of the report. Variant classification and interpretation are subject to professional judgment and may change for a variety of reasons including, but not limited to, updates in classification guidelines and availability of additional scientific and clinical information. It is important to check in with the laboratory annually for variant updates because new information regarding the variant and classification may become available over time.

Please visit QuestDiagnostics.com/VariantIQ for information about variant classification. For questions, please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463) to speak with a genomic science specialist.