ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.2500C>T (p.Gln834Ter)

dbSNP: rs122460158
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Neuberg Centre For Genomic Medicine, NCGM RCV000012255 SCV004047004 uncertain significance Developmental and epileptic encephalopathy, 2 criteria provided, single submitter clinical testing The missense variant c.2500C>T (p.Gln834Ter) in CDKL5 has been observed in affected individuals in literature (Nectoux J,2006). This variant has been reported to the ClinVar database as Pathogenic. The variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The nucleotide change in CDKL5 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic .
Invitae RCV003764559 SCV004571456 likely pathogenic Developmental and epileptic encephalopathy, 2; Angelman syndrome-like 2023-02-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln834*) in the CDKL5 gene. However, it is currently unclear if variants that occur in this region of the gene cause disease. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with CDKL5-related conditions (PMID: 16813600). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 11500). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000012255 SCV000032489 pathogenic Developmental and epileptic encephalopathy, 2 2006-07-01 no assertion criteria provided literature only
RettBASE RCV000133352 SCV000188363 pathogenic Atypical Rett syndrome 2014-03-13 no assertion criteria provided curation

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