Submissions for variant NM_001323289.2(CDKL5):c.786C>A (p.Tyr262Ter) (rs1555951146)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000579245	SCV000681153	pathogenic	not provided	2017-11-29	criteria provided, single submitter	clinical testing	The Y262X nonsense variant in the CDKL5 gene is predicted to cause loss of normal protein functioneither through protein truncation or nonsense-mediated mRNA decay. This variant is not observed in large population cohorts (Lek et al., 2016). Although this pathogenic variant has not been reported previously to our knowledge, its presence is consistent with the diagnosis of a CDKL5-related disorder in this individual.
Invitae	RCV001047013	SCV001210942	pathogenic	Early infantile epileptic encephalopathy 2; Angelman syndrome-like	2019-03-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr262*) 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 not been reported in the literature in individuals with CDKL5-related conditions. ClinVar contains an entry for this variant (Variation ID: 489166). Loss-of-function variants in CDKL5 are known to be pathogenic (PMID: 22872100). For these reasons, this variant has been classified as Pathogenic.