ClinVar Miner

Submissions for variant NM_000548.4(TSC2):c.5418T>G (p.Phe1806Leu) (rs200004126)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Human Development Section,National Institutes of Health RCV000034666 SCV000043549 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
Invitae RCV000206054 SCV000262341 uncertain significance Tuberous sclerosis 2 2018-05-30 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 1806 of the TSC2 protein (p.Phe1806Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs200004126, ExAC 0.005%) but has not been reported in the literature in individuals with a TSC2-related disease. ClinVar contains an entry for this variant (Variation ID: 41749). 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"). In summary, this is a rare missense change with uncertain impact on protein function. There is no indication that this variant causes disease, but the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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