Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000543191 | SCV000644231 | uncertain significance | Tuberous sclerosis 2 | 2023-12-07 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 45 of the TSC2 protein (p.Leu45Arg). 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: 467862). 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. |
| Ambry Genetics | RCV002384164 | SCV002694905 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-02-26 | criteria provided, single submitter | clinical testing | The p.L45R variant (also known as c.134T>G), located in coding exon 1 of the TSC2 gene, results from a T to G substitution at nucleotide position 134. The leucine at codon 45 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Prevention |
RCV003403302 | SCV004110395 | uncertain significance | TSC2-related condition | 2023-11-27 | criteria provided, single submitter | clinical testing | The TSC2 c.134T>G variant is predicted to result in the amino acid substitution p.Leu45Arg. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |