ClinVar Miner

Submissions for variant NM_025114.3(CEP290):c.1199C>T (p.Thr400Ile) (rs773578133)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000839270 SCV000981164 likely benign not provided 2018-04-27 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 RCV000526103 SCV000634635 uncertain significance Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis 2017-07-09 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 400 of the CEP290 protein (p.Thr400Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs773578133, ExAC 0.07%). This variant has not been reported in the literature in individuals with CEP290-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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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