Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001853088 | SCV002165917 | uncertain significance | Tuberous sclerosis 2 | 2021-10-02 | criteria provided, single submitter | clinical testing | This variant is also known as Pro1292Ser. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change does not substantially affect TSC2 function (PMID: 22903760). 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 not expected to disrupt TSC2 protein function. ClinVar contains an entry for this variant (Variation ID: 64947). This missense change has been observed in individual(s) with clinical features of tuberous sclerosis complex (PMID: 10732801, 22903760). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 1315 of the TSC2 protein (p.Pro1315Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine. |
| Ambry Genetics | RCV002371894 | SCV002624404 | likely benign | Hereditary cancer-predisposing syndrome | 2022-03-24 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Tuberous sclerosis database |
RCV000055150 | SCV000083368 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |