Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000796874 | SCV000936406 | uncertain significance | Tuberous sclerosis 2 | 2023-09-01 | criteria provided, single submitter | clinical testing | 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. 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: 643215). 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). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 923 of the TSC2 protein (p.Ser923Phe). |
| Ambry Genetics | RCV002440644 | SCV002751931 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-16 | criteria provided, single submitter | clinical testing | The p.S923F variant (also known as c.2768C>T), located in coding exon 24 of the TSC2 gene, results from a C to T substitution at nucleotide position 2768. The serine at codon 923 is replaced by phenylalanine, an amino acid with highly 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. |
| Center for Genomics, |
RCV003224474 | SCV003920600 | uncertain significance | Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2 | 2022-09-01 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature and is not present in large control databases. This variant is present in ClinVar (Variation ID:643215). Evolutionary conservation for this variant is unclear; computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |