ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.350A>G (p.Tyr117Cys) (rs1189749755)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497574 SCV000590150 likely pathogenic not provided 2017-06-07 criteria provided, single submitter clinical testing The Y117C variant in the CDKL5 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Y117C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Y117C variant is a non-conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function.We interpret Y117C as a likely pathogenic variant
Invitae RCV000812296 SCV000952606 uncertain significance Early infantile epileptic encephalopathy 2; Angelman syndrome-like 2018-12-31 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 117 of the CDKL5 protein (p.Tyr117Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CDKL5-related conditions. ClinVar contains an entry for this variant (Variation ID: 432427). 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. 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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