ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.585C>G (p.Ile195Met)

dbSNP: rs397515309
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Total submissions: 3
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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.
GeneDx 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.

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