Associated disorders

The TCS2 gene is associated with autosomal dominant tuberous sclerosis complex (TSC) (MedGen UID: 348170).

Pathogenic variants in the TSC2 gene are associated with ~66% of clinical cases of tuberous sclerosis complex.

The TSC2 gene encodes a protein called tuberin. Within cells, tuberin interacts with a protein called hamartin, which is produced from the TSC1 gene. Nutrient-sensing is central to essential cellular functions like cell growth, division, and survival. Tuberin inhibits nutrient-sensing pathways and could result in unrestrained or unorganized cell growth when not properly regulated.

  1. Northrup, H, et al. Tuberous Sclerosis Complex. 1999 Jul 13. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1220/ PMID: 20301399
  2. Au, KS, et al. Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States. Genet. Med. 2007; 9(2):88-100. doi: 10.1097GIM.0b013e31803068c7. PMID: 17304050
  3. Northrup, H, et al. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference. Pediatr. Neurol. 2013; 49(4):243-54. doi: 10.1016/j.pediatrneurol.2013.08.001. PMID: 24053982
  4. Crino, PB. mTOR signaling in epilepsy: insights from malformations of cortical development. Cold Spring Harb Perspect Med. 2015; 5(4):None. PMID: 25833943
  5. Zhang Y, et al. Coordinated regulation of protein synthesis and degradation by mTORC1. Nature. 2014 Sep 18;513(7518):440-3. PMID: 25043031
  6. Jones AC, et al. Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis. Am J Hum Genet. 1999 May;64(5):1305-15. PMID: 10205261
  7. Dabora SL, et al. Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. Am J Hum Genet. 2001 Jan;68(1):64-80. PMID: 11112665
  8. Sancak O, et al. Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype--phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex. Eur J Hum Genet. 2005 Jun;13(6):731-41. PMID: 15798777

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
TSC2 NM_000548.3