Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000796978 | SCV000936514 | uncertain significance | Tuberous sclerosis 1 | 2024-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 768 of the TSC1 protein (p.Arg768Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 643306). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TSC1 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 | RCV002424828 | SCV002731771 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-17 | criteria provided, single submitter | clinical testing | The p.R768C variant (also known as c.2302C>T), located in coding exon 16 of the TSC1 gene, results from a C to T substitution at nucleotide position 2302. The arginine at codon 768 is replaced by cysteine, an amino acid with highly dissimilar 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. |
| Gene |
RCV003327463 | SCV004034876 | uncertain significance | not provided | 2023-03-07 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18466115) |
| Baylor Genetics | RCV004569546 | SCV005054423 | uncertain significance | Isolated focal cortical dysplasia type II | 2023-11-09 | criteria provided, single submitter | clinical testing |