ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.1675C>T (p.Arg559Ter) (rs267608395)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000133328 SCV000191066 pathogenic not provided 2012-08-21 criteria provided, single submitter clinical testing The R559X mutation in the CDKL5 gene has been reported previously in association with early-onset epileptic encephalopathy (Sartori et al., 2009; Liang et al., 2011). This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. We interpret R559X as a disease-causing mutation, consistent with the diagnosis of epilepsy, hypotonia, and intellectual disability. This variant has been observed de novo without parental validation. This variant has been seen as a mosaic. The variant is found in INFANT-EPI panel(s).
Genetic Services Laboratory,University of Chicago RCV000145521 SCV000192609 pathogenic Early infantile epileptic encephalopathy 2 2013-02-08 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000145521 SCV000611255 pathogenic Early infantile epileptic encephalopathy 2 2017-05-18 criteria provided, single submitter clinical testing
Invitae RCV000694251 SCV000822686 pathogenic Early infantile epileptic encephalopathy 2; Angelman syndrome-like 2018-07-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg559*) in the CDKL5 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with epilepsy (PMID: 27770071, 27823948, 22872100) and to be de novo in an individual affected with suspected early onset encephalopathy (PMID: 19161156). ClinVar contains an entry for this variant (Variation ID: 143781). Loss-of-function variants in CDKL5 are known to be pathogenic (PMID: 22872100). For these reasons, this variant has been classified as Pathogenic.
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV000145521 SCV001164147 pathogenic Early infantile epileptic encephalopathy 2 2017-07-11 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000145521 SCV001428707 likely pathogenic Early infantile epileptic encephalopathy 2 2019-10-14 criteria provided, single submitter clinical testing This variant was identified as hemizygous
RettBASE RCV000169917 SCV000188337 pathogenic Atypical Rett syndrome 2014-03-13 no assertion criteria provided curation
RettBASE RCV000145521 SCV000222316 pathogenic Early infantile epileptic encephalopathy 2 2014-03-13 no assertion criteria provided curation
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes RCV000133328 SCV000778216 pathogenic not provided 2016-09-26 no assertion criteria provided clinical testing

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