Submissions for variant NM_001323289.2(CDKL5):c.1648C>T (p.Arg550Ter) (rs267608643)

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000133327	SCV000191065	pathogenic	not provided	2018-05-17	criteria provided, single submitter	clinical testing	The R550X nonsense variant in the CDKL5 gene has been reported previously in association with atypical Rett syndrome and CDKL5-related disorders (Pintaudi et al., 2008; Rademacher et al., 2011; Bahi-Buisson et al., 2012). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R550X variant is not observed in large population cohorts (Lek et al., 2016). The variant is found in EPILEPSY panel(s).
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000133327	SCV001246518	pathogenic	not provided	2018-11-01	criteria provided, single submitter	clinical testing
Invitae	RCV001244788	SCV001418032	pathogenic	Early infantile epileptic encephalopathy 2; Angelman syndrome-like	2019-10-23	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg550*) 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 several individuals affected with CDKL5-related conditions (PMID: 18063413, 21318334, 22678952). ClinVar contains an entry for this variant (Variation ID: 143780). Loss-of-function variants in CDKL5 are known to be pathogenic (PMID: 22872100). For these reasons, this variant has been classified as Pathogenic.
RettBASE	RCV000169916	SCV000188336	pathogenic	Atypical Rett syndrome	2014-03-13	no assertion criteria provided	curation
RettBASE	RCV000170009	SCV000222315	pathogenic	Early infantile epileptic encephalopathy 2	2014-03-13	no assertion criteria provided	curation