ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.1671dup (p.Arg558fs)

dbSNP: rs587783115
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000144786 SCV000191010 pathogenic not provided 2014-03-28 criteria provided, single submitter clinical testing The c.1671_1672insA (aka c.1671dupA) mutation in the CDKL5 gene has been reported previously in association with CDKL5-related disorders (Fehr et al., 2013). The duplication causes a frameshift starting with codon Arginine 558, changes this amino acid to a Threonine residue and creates a premature Stop codon at position 9 of the new reading frame, denoted p.Arg558ThrfsX9. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is found in INFANT-EPI panel(s).
Revvity Omics, Revvity RCV003137646 SCV003823104 likely pathogenic Developmental and epileptic encephalopathy, 2 2022-11-04 criteria provided, single submitter clinical testing
Centre for Population Genomics, CPG RCV004724918 SCV005335239 pathogenic CDKL5 disorder 2024-09-20 criteria provided, single submitter curation This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as pathogenic. At least the following criteria are met: Predicted to result in loss of function, and LOF is a known mechanism of disease (PVS1). This variant is absent from gnomAD v4 (PM2_Supporting). Has been observed in at least 2 individuals with phenotypes consistent with CDKL5 disorder (PS4_Supporting). PMID:25657822, Variation ID: 156643

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