Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000693935 | SCV000822358 | uncertain significance | Benign neonatal seizures | 2024-11-19 | 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 695 of the KCNQ3 protein (p.Pro695Leu). This variant is present in population databases (rs760983146, gnomAD 0.005%). This missense change has been observed in individual(s) with familial centrotemporal spikes (PMID: 18625963). ClinVar contains an entry for this variant (Variation ID: 572531). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt KCNQ3 protein function with a negative predictive value of 95%. Experimental studies have shown that this missense change affects KCNQ3 function (PMID: 18625963). 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. |