Submissions for variant NM_001323289.2(CDKL5):c.549_552del (p.Leu184fs)

dbSNP: rs587783111

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000144782	SCV000191006	pathogenic	not provided	2013-03-18	criteria provided, single submitter	clinical testing	The c.549_552delACTT mutation in the CDKL5 gene causes a frameshift starting with codon Leucine 184, changes this amino acid to an Alanine residue and creates a premature Stop codon at position 43 of the new reading frame, denoted p.Leu184AlafsX43. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Although this mutation has not been previously reported to our knowledge, other frameshift mutations have been reported in CDKL5 in association with epilepsy. The variant is found in INFANT-EPI panel(s).
Invitae	RCV002515944	SCV003461837	pathogenic	Developmental and epileptic encephalopathy, 2; Angelman syndrome-like	2022-04-07	criteria provided, single submitter	clinical testing	This premature translational stop signal has been observed in individual(s) with clinical features of CDKL5-related conditions (PMID: 29655203). This sequence change creates a premature translational stop signal (p.Leu184Alafs*43) in the CDKL5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDKL5 are known to be pathogenic (PMID: 22872100). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 156639). For these reasons, this variant has been classified as Pathogenic.