ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2218A>G (p.Met740Val)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Gharavi Laboratory,Columbia University RCV000722723 SCV000853854 uncertain significance not provided 2018-09-16 no assertion criteria provided research
Invitae RCV000691766 SCV000819557 uncertain significance Tuberous sclerosis 2 2018-10-13 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 740 of the TSC2 protein (p.Met740Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TSC2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; 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 and their clinical significance is uncertain. 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.

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