Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001379013 | SCV001576727 | pathogenic | Developmental and epileptic encephalopathy, 32 | 2023-10-18 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 407 of the KCNA2 protein (p.Pro407Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of KCNA2-related conditions (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 1067683). 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 KCNA2 protein function. This variant disrupts the p.Pro407 amino acid residue in KCNA2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 33802230; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Department of Developmental Neurology, |
RCV001379013 | SCV004100899 | not provided | Developmental and epileptic encephalopathy, 32 | no assertion provided | phenotyping only |