Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
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). |
Gene |
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 |