Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001852889 | SCV002313094 | likely pathogenic | Tuberous sclerosis 2 | 2021-08-11 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with threonine at codon 1497 of the TSC2 protein (p.Pro1497Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with tuberous sclerosis (Invitae). ClinVar contains an entry for this variant (Variation ID: 49490). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Pro1497 amino acid residue in TSC2. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TSC2 protein function. |
Gene |
RCV003441731 | SCV004168104 | pathogenic | not provided | 2023-10-02 | criteria provided, single submitter | clinical testing | Reported previously in a familial case of tuberous sclerosis complex; however, no inheritance or family information was provided (PMID: 17304050); Published functional studies demonstrate a damaging effect and show that this variant reduces TSC2 signal and increases T389/S6K phosphorylation (PMID: 21309039); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 37311496, 17304050, 12136241, 21309039) |
Tuberous sclerosis database |
RCV000042750 | SCV000066545 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |