Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001068526 | SCV001233642 | uncertain significance | Tuberous sclerosis 2 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with cysteine at codon 1647 of the TSC2 protein (p.Ser1647Cys). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | RCV002339340 | SCV002641263 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-08 | criteria provided, single submitter | clinical testing | The p.S1647C variant (also known as c.4940C>G), located in coding exon 37 of the TSC2 gene, results from a C to G substitution at nucleotide position 4940. The serine at codon 1647 is replaced by cysteine, an amino acid with dissimilar 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. |