ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.119C>T (p.Ala40Val) (rs122460159)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000699210 SCV000827910 pathogenic Early infantile epileptic encephalopathy 2; Angelman syndrome-like 2019-03-19 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 40 of the CDKL5 protein (p.Ala40Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with CDKL5-related disorders (PMID: 17993579, 25819767, 22678952, 19780792). ClinVar contains an entry for this variant (Variation ID: 11502). Experimental studies have shown that this missense change causes mislocalization of the mutant protein to the nucleus (PMID: 17993579, 19793311). Variants that disrupt the p.Ala40 amino acid residue in CDKL5 have been observed in affected individuals (PMID: 27848944). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV000012257 SCV001164152 pathogenic Early infantile epileptic encephalopathy 2 2017-06-29 criteria provided, single submitter clinical testing
OMIM RCV000012257 SCV000032491 pathogenic Early infantile epileptic encephalopathy 2 2009-10-01 no assertion criteria provided literature only
RettBASE RCV000133317 SCV000188326 pathogenic Atypical Rett syndrome 2014-03-13 no assertion criteria provided curation In vitro study shows mislocalisation of CDKL5 in the cytoplasm
RettBASE RCV000012257 SCV000222299 pathogenic Early infantile epileptic encephalopathy 2 2014-03-13 no assertion criteria provided curation In vitro study shows mislocalisation of CDKL5 in the cytoplasm

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