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

dbSNP: rs267608395

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000133328	SCV000191066	pathogenic	not provided	2020-08-04	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 27823948, 22670135, 22779007, 23064044, 25525159, 19161156, 27770071, 28837158, 27081548, 23583054, 30928302, 30460546, 31313283, 22872100, 21770923)
Genetic Services Laboratory, University of Chicago	RCV000145521	SCV000192609	pathogenic	Developmental and epileptic encephalopathy, 2	2013-02-08	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000145521	SCV000611255	pathogenic	Developmental and epileptic encephalopathy, 2	2017-05-18	criteria provided, single submitter	clinical testing
Invitae	RCV000694251	SCV000822686	pathogenic	Developmental and epileptic encephalopathy, 2; Angelman syndrome-like	2021-04-24	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CDKL5 are known to be pathogenic (PMID: 22872100). 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). This variant is not present in population databases (ExAC no frequency). 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.
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV000145521	SCV001164147	pathogenic	Developmental and 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	Developmental and epileptic encephalopathy, 2	2019-10-14	criteria provided, single submitter	clinical testing	This variant was identified as hemizygous
Institute of Human Genetics, University Hospital of Duesseldorf	RCV000145521	SCV004171127	pathogenic	Developmental and epileptic encephalopathy, 2		criteria provided, single submitter	not provided
RettBASE	RCV000169917	SCV000188337	pathogenic	Atypical Rett syndrome	2014-03-13	no assertion criteria provided	curation
RettBASE	RCV000145521	SCV000222316	pathogenic	Developmental and 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