Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000691063 | SCV000818803 | uncertain significance | Tuberous sclerosis 2 | 2022-10-13 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 455 of the TSC2 protein (p.Ser455Asn). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 570246). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV002386192 | SCV002702903 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-19 | criteria provided, single submitter | clinical testing | The p.S455N variant (also known as c.1364G>A), located in coding exon 13 of the TSC2 gene, results from a G to A substitution at nucleotide position 1364. The serine at codon 455 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is poorly 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. |