ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.739A>G (p.Ile247Val) (rs774526017)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000405414 SCV000395566 uncertain significance Tuberous sclerosis syndrome 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000433208 SCV000515643 likely benign not specified 2015-12-21 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 RCV000465522 SCV000544430 uncertain significance Tuberous sclerosis 2 2016-11-04 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 247 of the TSC2 protein (p.Ile247Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs774526017, ExAC 0.01%) but has not been reported in the literature in individuals with a TSC2-related disease. 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 valine 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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