Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000795714 | SCV000935184 | uncertain significance | Tuberous sclerosis 2 | 2023-11-18 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 1289 of the TSC2 protein (p.Arg1289Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 642278). 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 with a negative predictive value of 95%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. |
Baylor Genetics | RCV003467351 | SCV004205097 | uncertain significance | Isolated focal cortical dysplasia type II | 2023-05-11 | criteria provided, single submitter | clinical testing |