Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000658260 | SCV000780031 | likely benign | not provided | 2020-09-03 | criteria provided, single submitter | clinical testing | Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This substitution is predicted to be within the C-terminal cytoplasmic domain (UniProt, Millichap JJ 2016 and Soldovieri 2007) |
Invitae | RCV001861170 | SCV002201366 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2023-10-16 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 737 of the KCNQ2 protein (p.Gly737Ser). This variant is present in population databases (rs755013341, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with KCNQ2-related conditions. ClinVar contains an entry for this variant (Variation ID: 339330). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on KCNQ2 function (PMID: 35104249). 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. |
Channelopathy- |
RCV003315338 | SCV004015037 | not provided | Complex neurodevelopmental disorder | no assertion provided | literature only |