ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.532C>G (p.Arg178Gly)

dbSNP: rs267608493
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001383655 SCV001582875 pathogenic Developmental and epileptic encephalopathy, 2; Angelman syndrome-like 2020-09-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 178 of the CDKL5 protein (p.Arg178Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of CDKL5-related conditions (Invitae). In at least one individual the variant was observed to be de novo. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Arg178 amino acid residue in CDKL5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18809835, 19793311, 21770923, 26482601, 26993267). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV002221628 SCV002498889 pathogenic not provided 2022-03-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18809835, 26482601, 19793311, 21770923, 26993267)

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