Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clinical Molecular Genetics Laboratory, |
RCV000853534 | SCV000995916 | likely pathogenic | Seizures, benign familial neonatal, 1 | 2019-10-04 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001217360 | SCV001389196 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2022-11-23 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 692196). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Asp259 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been observed in individuals with KCNQ2-related conditions (PMID: 27535030), which suggests that this may be a clinically significant amino acid residue. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KCNQ2 protein function. This missense change has been observed in individual(s) with benign familial epilepsy (PMID: 29215089). 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 aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 259 of the KCNQ2 protein (p.Asp259Asn). |