ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.533G>C (p.Arg178Pro) (rs267606715)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001035195 SCV001198510 pathogenic Early infantile epileptic encephalopathy 2; Angelman syndrome-like 2019-12-04 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 178 of the CDKL5 protein (p.Arg178Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. 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 condition (PMID: 18809835, 19793311, 30776697). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 18450). This variant has been reported to affect CDKL5 protein function (PMID: 19793311). This variant disrupts the p.p.Arg178 amino acid residue in CDKL5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19793311, 22678952, 19362436, 25657822, 26482601, 29190809). 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.
OMIM RCV000012262 SCV000032496 pathogenic Early infantile epileptic encephalopathy 2 2009-10-01 no assertion criteria provided literature only
RettBASE RCV000012262 SCV000188389 pathogenic Early infantile epileptic encephalopathy 2 2014-03-13 no assertion criteria provided curation Highly conserved residue, one male patient (healthy mother not carrier), de novo in second patient (female); In silico prediction: SIFT = deleterious, MutationTaster = disease-causing, PolyPhen2 = probably damaging, AlignGVGD = benign (C0)

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