Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001059625 | SCV001224252 | uncertain significance | Tuberous sclerosis 1 | 2020-11-06 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with TSC1-related conditions. 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with glycine at codon 295 of the TSC1 protein (p.Ser295Gly). The serine residue is moderately conserved and there is a small physicochemical difference between serine and glycine. |
| Ambry Genetics | RCV003160480 | SCV003882125 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-01 | criteria provided, single submitter | clinical testing | The p.S295G variant (also known as c.883A>G), located in coding exon 7 of the TSC1 gene, results from an A to G substitution at nucleotide position 883. The serine at codon 295 is replaced by glycine, 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. |