ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.1564T>G (p.Leu522Val) (rs781427744)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000502210 SCV000593963 uncertain significance not specified 2016-08-19 criteria provided, single submitter clinical testing
Invitae RCV000793868 SCV000933245 uncertain significance Early infantile epileptic encephalopathy 2; Angelman syndrome-like 2019-11-16 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 522 of the CDKL5 protein (p.Leu522Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs781427744, ExAC 0.002%). This variant has not been reported in the literature in individuals with CDKL5-related disease. ClinVar contains an entry for this variant (Variation ID: 434664). 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.
GeneDx RCV000831115 SCV000972856 likely benign not provided 2018-06-15 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000831115 SCV001246517 uncertain significance not provided 2019-12-01 criteria provided, single submitter clinical testing

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