Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000461472 | SCV000544555 | uncertain significance | Tuberous sclerosis 2 | 2020-06-12 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with arginine at codon 1290 of the TSC2 protein (p.Ser1290Arg). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and arginine. This variant has not been reported in the literature in individuals with TSC2-related disease. ClinVar contains an entry for this variant (Variation ID: 406113). 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). |
Fulgent Genetics, |
RCV002480364 | SCV002777190 | uncertain significance | Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2 | 2021-08-04 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003168765 | SCV003862747 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-23 | criteria provided, single submitter | clinical testing | The p.S1290R variant (also known as c.3870C>G), located in coding exon 31 of the TSC2 gene, results from a C to G substitution at nucleotide position 3870. The serine at codon 1290 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |