Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001861356 | SCV002236642 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2023-04-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Leu351 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects KCNQ2 function (PMID: 24375629). 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. ClinVar contains an entry for this variant (Variation ID: 369779). This missense change has been observed in individual(s) with KCNQ2-related conditions (PMID: 24375629). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 351 of the KCNQ2 protein (p.Leu351Phe). |
| Gene |
RCV000678159 | SCV000484604 | not provided | Seizures, benign familial neonatal, 1 | no assertion provided | literature only | BFNE (benign familial neonatal epilepsy) |