• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
TSC2 (HGNC:12363) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
TSC complex subunit 2
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
TSC4
Alias symbols
tuberin, LAM, PPP1R160
%HI
10.92(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.07(Read more about gnomAD LOEUF score)
Cytoband
16p13.3
Genomic Coordinates
GRCh37/hg19: chr16:2097986-2139492 NCBI Ensembl UCSC
GRCh38/hg38: chr16:2047985-2089491 NCBI Ensembl UCSC
MANE Select Transcript
NM_000548.5 ENST00000219476.9 (Read more about MANE Select)
Function
Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12172553, PubMed:12271141, PubMed:12906785, PubMed:12842888, PubMed:28215400, PubMed:35772404, PubMed:15340059, PubMed:22819219, PubMed:24529379, PubMed:33436626). Within the TSC-TBC complex... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-26920
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
06/10/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 31525612
    Published in 2019, Lin et al. used Sanger sequencing and Multiplex ligation-dependent probe amplification (MLPA) on 77 unrelated Chinese individuals diagnosed with Tuberous sclerosis complex to assess variants in TSC1 and TSC2. This study found 3 nonsense variants, 6 splicing variants, a total of 18 frameshift variants, and 2 large deletions in TSC2. Additionally, 51.9% of the cohort (39 individuals) had de novo variants in TSC2.
  • PUBMED: 10205261
    Published in 1999, Jones et al. used PCR and single-strand confirmation polymorphism (SSCP) and Heteroduplex analysis on 150 Tuberous sclerosis complex patients and their families to assess variants in TSC1 and TSC2. The methodology found that 9 cases of variants in TSC2 were familial; 88 other cases involving TSC2 variants were sporadic. This study identified 20 nonsense variants, 21 small insertions or deletions, 8 splice variants, 5 in-frame deletions, and 8 large intragenic deletions in TSC2.
  • PUBMED: 29932062
    Published in 2014, Glushkova et al. used Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) on 17 unrelated individuals who met the clinical description for Tuberous sclerosis complex (TSC) to search for variants in TSC1 and TSC2. This study identified 2 nonsense variants, 3 frame-shift variants, 1 splice variant, and 1 large deletion in TSC2. In terms of inheritance, 4 individuals had a de novo variant.
HI Evidence Comments:
Variants involving the TSC2 gene, including intragenic and whole-gene heterozygous deletions, cause tuberous sclerosis complex (TSC). TSC is an autosomal dominant multi-system disorder, which affects 1 in 6000 people. About half of these patients are affected by intellectual disability. PMID 11030407: Reviewed 222 TSC2 mutations that had been reported in the literature. Large genomic deletions (intragenic and whole-gene) accounted for 16% of all variants reported. Larger heterozygous deletions, involving the TSC2 and adjacent PKD1 gene, result in the TSC2/PKD1 contiguous gene syndrome (PKDTS) [PMIDs 22169896, 18818683, 14695542, 17185137). PKDTS has been identified in patients with tuberous sclerosis complex (TSC) and early-onset severe autosomal dominant polycystic kidney disease (ADPKD).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
No literature identified

Genomic View

Select assembly: (NC_000016.9) (NC_000016.10)