ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.2209G>A (p.Gly737Ser)

gnomAD frequency: 0.00001  dbSNP: rs755013341
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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)
Labcorp Genetics (formerly Invitae), Labcorp RCV001861170 SCV002201366 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2025-01-28 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). 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 KCNQ2 protein function with a negative predictive value of 95%. 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-Associated Epilepsy Research Center RCV003315338 SCV004015037 not provided Complex neurodevelopmental disorder no assertion provided literature only

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