Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000519627 | SCV000619471 | uncertain significance | not specified | 2017-07-21 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the KCNQ3 gene. The c.1249_1250delGAinsAT variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.1249_1250delGAinsAT variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.1249_1250delGAinsAT variant results in an in-frame deletion of a single Glutamic acid residue and the insertion of a single Methionine residue, denoted p.E417M. This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution alters residues that are conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Fulgent Genetics, |
RCV000765989 | SCV000897421 | uncertain significance | Seizures, benign familial neonatal, 2 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001853644 | SCV002175935 | uncertain significance | Benign neonatal seizures | 2023-06-05 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with KCNQ3-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces glutamic acid, which is acidic and polar, with methionine, which is neutral and non-polar, at codon 417 of the KCNQ3 protein (p.Glu417Met). ClinVar contains an entry for this variant (Variation ID: 450849). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. |