Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000659288 | SCV000781092 | likely benign | West syndrome | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002536338 | SCV002972111 | uncertain significance | Developmental and epileptic encephalopathy, 2; Angelman syndrome-like | 2022-10-21 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 not expected to disrupt CDKL5 protein function. ClinVar contains an entry for this variant (Variation ID: 547186). This variant has not been reported in the literature in individuals affected with CDKL5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 448 of the CDKL5 protein (p.Met448Ile). |