ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.583T>G (p.Trp195Gly) (rs1569215594)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000687369 SCV000814932 pathogenic Early infantile epileptic encephalopathy 2; Angelman syndrome-like 2018-04-05 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with glycine at codon 195 of the CDKL5 protein (p.Trp195Gly). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in individuals affected with infantile epilepsy (Invitae). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. A different missense substitution at this codon (p.Trp195Arg) has been reported in an individual affected with intellectual disability, hypotonia, manual dyspaxia, hand stereotype stereotypies, and absent speech (PMID: 21482751). For these reasons, this variant has been classified as Pathogenic.

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