Malformations of cortical development

Gene: TSC2

Red List (low evidence)

TSC2 (TSC complex subunit 2)
EnsemblGeneIds (GRCh38): ENSG00000103197
EnsemblGeneIds (GRCh37): ENSG00000103197
OMIM: 191092, Gene2Phenotype
TSC2 is in 26 panels

1 review

Ellen McDonagh (Genomics England Curator)

Comment on list classification: Should remain red at this stage, as as only one reported case in PMID: 28215400, though there is more evidence in TSC1 which is in the same pathway.
Created: 22 Sep 2017, 2:57 p.m.
PMID:19175396 reported sequence alterations in the TSC1 and TSC2 genes in lesional brain tissue and blood of Focal cortical dysplasia patients are found in a similar frequency to that of a normal population. A more recent publication (PMID: 28215400) provides evidence for somatic brian mutations in TSC1 and TSC2 to be implicated in FCD2. They took 40 patients who were negative for MTOR mutations, and found candidate causative brain somatic variants in TSC1 or TSC2 in 5 patients (3 different missense variants). In vitro assays provided evidence to show that the mutations induced activation of mTOR kinase by disturbing the formation or function of the TSC1-TSC2 complex. Using in utero CRISPR-Cas9 somatic genome-editing system, a focal cortical disruption of the TSC1-TSC2 complex, encoded by Tsc1 and Tsc2 was reported to cause spontaneous behavioral seizures as well as migration defects and cytomegalic neurons, consistent with the neuropathological phenotype of individuals with FCD2. Two of the 3 variants reported were found at a low frequency in ExAC Browser (1.65x10-5 and 3.34x10-5). One missense was reported in TSC2, in one patient.
Created: 22 Sep 2017, 2:55 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Focal cortical dysplasia, type II, somatic 607341


Mode of pathogenicity

History Filter Activity

22 Sep 2017, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

22 Sep 2017, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

TSC2 was added to Malformations of cortical developmentpanel. Sources: Literature

22 Sep 2017, Gel status: 0


Ellen McDonagh (Genomics England Curator)

TSC2 was created by ellenmcdonagh