ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.1064G>A (p.Arg355Gln)

gnomAD frequency: 0.00006  dbSNP: rs189400843
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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 RCV003168974 SCV003853572 benign CDKL5 disorder 2023-02-20 reviewed by expert panel curation The allele frequency of the p.Arg355Gln variant in CDKL5 is 0.011% in African sub population in gnomAD, which is high enough to be classified as likely benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). Additionally, the p.Arg355Gln variant is observed in at least 2 unaffected individuals (internal database - GeneDx, internal database - Invitae) (BS2) and the variant is found in at least 2 patients with an alternate molecular basis of disease (internal database - GeneDx, internal database - Invitae) (BP5). In summary, the p.Arg355Gln variant in CDKL5 is classified as Benign for CDKL5-associated disorder based on the ACMG/AMP criteria (BS1, BS2, BP5).
GeneDx RCV000481786 SCV000573182 uncertain significance not provided 2017-02-08 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CDKL5 gene. The R355Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R355Q variant is observed in 2/8,514 (0.02%) alleles from individuals of African background, including 1 hemizygous individual in the ExAC dataset (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R355Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001456035 SCV001659810 likely benign Developmental and epileptic encephalopathy, 2; Angelman syndrome-like 2023-11-27 criteria provided, single submitter clinical testing

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