Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000797717 | SCV000937293 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2022-04-04 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 277 of the KCNQ2 protein (p.Thr277Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of KCNQ2-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: 643905). 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 KCNQ2 protein function. This variant disrupts the p.Thr277 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30182498; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. |