Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000489788 | SCV000576696 | uncertain significance | not provided | 2017-04-21 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the CDKL5 gene. The R858C variant was reported previously as a potentially disruptive variant in a patient with epileptic encephalopathy (Carvill et al., 2013). However, additional clinical information was not provided and functional characterization of the variant was not completed. The R858C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R858C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with CDKL5-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV002063831 | SCV002431582 | likely benign | Developmental and epileptic encephalopathy, 2; Angelman syndrome-like | 2024-01-25 | criteria provided, single submitter | clinical testing |