ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.1211_1212dup (p.Leu405fs) (rs1555951981)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel, ClinGen RCV001507070 SCV001712043 pathogenic CDKL5 disorder 2021-03-26 reviewed by expert panel curation The p.Leu405Thrfs variant in CDKL5 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene in which loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1). This variant has been detected in at least one individual with CDKL5 disorder (ClinVar) (PS4_supporting). This variant is absent from the gnomAD (PM2_supporting). In summary, the p.Leu405Thrfs variant in CDKL5 is classified as Pathogenic for CDKL5 disorder based on the ACMG/AMP criteria (PVS1, PM2_supporting, PS4_supporting).
GeneDx RCV000487335 SCV000572651 pathogenic not provided 2017-01-19 criteria provided, single submitter clinical testing The c.1211_1212dupAC pathogenic variant in the CDKL5 gene causes a frameshift starting with codon Leucine 405, changes this amino acid to a Threonine residue and creates a premature Stop codon at position 89 of the new reading frame, denoted p.Leu405ThrfsX89. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, the c.1211_1212dupAC variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Ambry Genetics RCV000623064 SCV000741169 pathogenic Inborn genetic diseases 2015-11-10 criteria provided, single submitter clinical testing

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