Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003235465 | SCV003933680 | likely pathogenic | CDKL5 disorder | 2023-04-14 | reviewed by expert panel | curation | The p.Leu97Pro variant in CDKL5 occurs in the de novo state (biological parentage confirmed) in an individual (GeneDx Internal Database) (PS2). The p.Leu97Pro variant in CDKL5 is absent from gnomAD (PM2_supporting). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). In summary, the p.Leu97Pro variant in CDKL5 is classified as likely pathogenic for a CDKL5-related disorder based on the ACMG/AMP criteria (PS2, PM2_supporting, PP3). |
Laboratory of Inherited Metabolic Diseases, |
RCV001089706 | SCV001245190 | likely pathogenic | Developmental and epileptic encephalopathy, 2 | 2020-02-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001301919 | SCV001491104 | pathogenic | Developmental and epileptic encephalopathy, 2; Angelman syndrome-like | 2021-04-15 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CDKL5 protein function. This variant has been observed in individual(s) with clinical features of CDKL5-related conditions (Invitae, external communication). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 870171). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 97 of the CDKL5 protein (p.Leu97Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. |