Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001227429 | SCV001399788 | uncertain significance | Tuberous sclerosis 1 | 2019-10-04 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with threonine at codon 838 of the TSC1 protein (p.Ser838Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine. 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TSC1-related conditions. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV002429968 | SCV002744283 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-22 | criteria provided, single submitter | clinical testing | The p.S838T variant (also known as c.2513G>C), located in coding exon 18 of the TSC1 gene, results from a G to C substitution at nucleotide position 2513. The serine at codon 838 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. 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. |