Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000704748 | SCV000833710 | uncertain significance | Tuberous sclerosis 2 | 2019-07-02 | criteria provided, single submitter | clinical testing | 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TSC2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with methionine at codon 195 of the TSC2 protein (p.Ile195Met). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and methionine. |
Gene |
RCV002473125 | SCV002770129 | uncertain significance | not provided | 2022-06-20 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18466115) |
Ambry Genetics | RCV003303186 | SCV003998300 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-27 | criteria provided, single submitter | clinical testing | The p.I195M variant (also known as c.585C>G), located in coding exon 5 of the TSC2 gene, results from a C to G substitution at nucleotide position 585. The isoleucine at codon 195 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well 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. |