Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000190077 | SCV000243752 | likely benign | not specified | 2014-10-01 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
| Invitae | RCV000644198 | SCV000765888 | uncertain significance | Tuberous sclerosis 2 | 2023-12-17 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1142 of the TSC2 protein (p.Leu1142Pro). 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: 207784). 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%. 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. |
| Genome- |
RCV000644198 | SCV002039748 | likely benign | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002453704 | SCV002614351 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-05 | criteria provided, single submitter | clinical testing | The p.L1142P variant (also known as c.3425T>C), located in coding exon 29 of the TSC2 gene, results from a T to C substitution at nucleotide position 3425. The leucine at codon 1142 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |