ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2968A>G (p.Arg990Gly)

gnomAD frequency: 0.00002  dbSNP: rs753730009
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189913 SCV000243573 likely benign not specified 2014-02-05 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000807950 SCV000948030 uncertain significance Tuberous sclerosis 2 2024-01-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 990 of the TSC2 protein (p.Arg990Gly). This variant is present in population databases (rs753730009, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 207675). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 RCV001017697 SCV001178819 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-20 criteria provided, single submitter clinical testing The p.R990G variant (also known as c.2968A>G), located in coding exon 26 of the TSC2 gene, results from an A to G substitution at nucleotide position 2968. The arginine at codon 990 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000807950 SCV002039705 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing

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