Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000644224 | SCV000765915 | uncertain significance | Tuberous sclerosis 2 | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1032 of the TSC2 protein (p.Arg1032Gln). This variant is present in population databases (rs45491698, gnomAD 0.0009%). 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: 535975). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TSC2 protein function. This variant disrupts the p.Arg1032 amino acid residue in TSC2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21309039, 21520333). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Ambry Genetics | RCV002325263 | SCV002608286 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-18 | criteria provided, single submitter | clinical testing | The p.R1032Q variant (also known as c.3095G>A), located in coding exon 26 of the TSC2 gene, results from a G to A substitution at nucleotide position 3095. The arginine at codon 1032 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Genetics and Molecular Pathology, |
RCV000644224 | SCV002761743 | uncertain significance | Tuberous sclerosis 2 | 2021-09-02 | criteria provided, single submitter | clinical testing |