Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001055610 | SCV001220010 | likely pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2022-07-19 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Trp270 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30478917). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 851253). This missense change has been observed in individual(s) with KCNQ2-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 270 of the KCNQ2 protein (p.Trp270Cys). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |