Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000187916 | SCV000241518 | pathogenic | not provided | 2018-12-18 | criteria provided, single submitter | clinical testing | p.Pro561Leu (CCC>CTC): c.1682 C>T in exon 15 in the KCNQ2 gene (NM_172107.2). The P561L mutation in the KCNQ2 gene has been reported previously in association with Ohtahara syndrome (Kato et al., 2013). The P561L mutation was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P561L mutation is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is well-conserved across species. In silico analysis predicts this mutation is probably damaging to the protein structure/function. Missense mutations in nearby residues (R560W and D563E) have been reported in association with neonatal epileptic encephalopathy and Ohtahara syndrome, supporting the functional importance of this region of the protein. We interpret P561L as a disease-causing mutation. The variant is found in ,KCNQ2 panel(s). |
Invitae | RCV002517873 | SCV003443966 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2022-06-08 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 561 of the KCNQ2 protein (p.Pro561Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Ohtahara syndrome (PMID: 23621294). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 205916). 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. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000678189 | SCV000484638 | not provided | Developmental and epileptic encephalopathy, 7 | no assertion provided | literature only | EE (epileptic encephalopathy) |