Submissions for variant NM_001323289.2(CDKL5):c.1296_1298del (p.Lys432_Tyr433delinsAsn)

dbSNP: rs1555951997

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV001507063	SCV001712032	uncertain significance	CDKL5 disorder	2021-03-26	reviewed by expert panel	curation	The p.Lys432_Tyr433delinsAsn variant in CDKL5 is absent from gnomAD (PM2_supporting). The p.Lys432_Tyr433delinsAsn variant causes a change in the length of 1 amino acid in the protein due to an in-frame deletion or insertion in a non-repeat region of CDKL5 (PM4_supporting). In summary, p.Lys432_Tyr433delinsAsn variant in CDKL5 is classified as a variant of uncertain significance based on the ACMG/AMP criteria (PM2_supporting, PM4_supporting).
Genetic Services Laboratory, University of Chicago	RCV000504427	SCV000593961	uncertain significance	not specified	2015-11-12	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002524164	SCV003208841	uncertain significance	Developmental and epileptic encephalopathy, 2; Angelman syndrome-like	2022-05-31	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 434662). This variant has not been reported in the literature in individuals affected with CDKL5-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.1296_1298del, results in the deletion of one amino acid(s) of the CDKL5 protein (p.Lys432_Tyr433delinsAsn), but otherwise preserves the integrity of the reading frame.