• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
TSC1 (HGNC:12362) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
TSC complex subunit 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
TSC
Alias symbols
KIAA0243, LAM, hamartin
%HI
11.9(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.12(Read more about gnomAD LOEUF score)
Cytoband
9q34
Genomic Coordinates
GRCh37/hg19: chr9:135766736-135820003 NCBI Ensembl UCSC
GRCh38/hg38: chr9:132891349-132945378 NCBI Ensembl UCSC
MANE Select Transcript
NM_000368.5 ENST00000298552.9 (Read more about MANE Select)
Function
Non-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:12906785, PubMed:12271141, PubMed:28215400, PubMed:15340059, PubMed:24529379). The TSC-TBC complex acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-33751
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
10/13/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 32917966
    Meng Y et al. (2020) performed targeted exome sequencing of 4800 genes in 347 Chinese patients with a clinically suspected diagnosis of tuberous sclerosis. Among the nonsynonymous variants detected, there were 51 TSC1 variants identified that were classified based on ACMG guidelines as either pathogenic, likely pathogenic, or variants of uncertain significance. Of these TSC1 variants, 37 were nonsense, frameshift, or canonical splice site.
  • PUBMED: 23389244
    Niida Y et al. (2013) sequenced the coding regions of TSC1 and TSC2 in 57 Japanese patients with tuberous sclerosis (46 with a definite and 11 with a suspected diagnosis). Eleven TSC1 variants were identified, including 1 missense variant, 9 loss-of-function (frameshift, nonsense, and canonical splice site) variants, and 1 large deletion of exons 17-19 (by long PCR).
  • PUBMED: 17304050
    Au KS et al. (2007) sequenced all the coding regions of TSC1 and TSC2 in 368 patients in the United States with a clinical diagnosis of tuberous sclerosis. Among these patients, 61 TSC1 variants were identified. Of these 61 variants, 21 were nonsense variants. Another 39 were deletion, insertion, splice alternative, or splice deletion variants, but it was not indicated if these would cause a frameshift or loss of canonical splice site.
HI Evidence Comments:
Although the evidence presented here is specific to the tuberous sclerosis phenotype, variants in TSC1 have also been observed in individuals with isolated lymphangioleiomyomatosis (OMIM #606690). Somatic variants in TSC1 have been observed in individuals with focal cortical dysplasia, type II (OMIM #607341). Of note, both of these are features of tuberous sclerosis (PMID 20301399).

Triplosensitivity (TS) Score Details

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

Genomic View

Select assembly: (NC_000009.11) (NC_000009.12)