Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000644099 | SCV000765789 | uncertain significance | Tuberous sclerosis 2 | 2022-02-08 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 394 of the TSC2 protein (p.Leu394Val). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: 535881). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). |
| Ambry Genetics | RCV003162909 | SCV003911455 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-16 | criteria provided, single submitter | clinical testing | The p.L394V variant (also known as c.1180C>G), located in coding exon 11 of the TSC2 gene, results from a C to G substitution at nucleotide position 1180. The leucine at codon 394 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice donor site. RNA studies have demonstrated that this alteration results in an incomplete splice defect; the clinical impact of this abnormal splicing is unknown at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003465406 | SCV004206897 | uncertain significance | Isolated focal cortical dysplasia type II | 2023-06-25 | criteria provided, single submitter | clinical testing |