ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.587C>T (p.Ser196Leu) (rs267608501)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000145544 SCV000192637 pathogenic Early infantile epileptic encephalopathy 2 2013-02-08 criteria provided, single submitter clinical testing
Neurogenetics Laboratory - MEYER,AOU Meyer RCV000416982 SCV000494535 pathogenic Epileptic encephalopathy 2016-11-16 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000431821 SCV000511415 pathogenic not provided 2016-09-15 criteria provided, single submitter clinical testing
Invitae RCV000812193 SCV000952498 likely pathogenic Early infantile epileptic encephalopathy 2; Angelman syndrome-like 2018-08-20 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 196 of the CDKL5 protein (p.Ser196Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual with epileptic encephalopathy (PMID: 20397747). ClinVar contains an entry for this variant (Variation ID: 143827). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
RettBASE RCV000145544 SCV000188393 likely pathogenic Early infantile epileptic encephalopathy 2 2014-03-13 no assertion criteria provided curation In silico prediction: SIFT = deleterious, MutationTaster = disease-causing, PolyPhen2 = probably damaging, AlignGVGD = pathogenic (C65)

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