ClinVar Miner

Submissions for variant NM_004519.4(KCNQ3):c.1706A>G (p.Asp569Gly)

gnomAD frequency: 0.00002  dbSNP: rs372671883
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001769408 SCV002001282 uncertain significance not provided 2021-07-08 criteria provided, single submitter clinical testing Reported in the heterozygous state in a patient with epilepsy and low average IQ who also harbored a pathogenic variant in the SCN1A gene (de Lange et al., 2020); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this variant has a deleterious effect on splicing; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32032478, 27535533)
Labcorp Genetics (formerly Invitae), Labcorp RCV001885050 SCV002171410 uncertain significance Benign neonatal seizures 2024-06-04 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 569 of the KCNQ3 protein (p.Asp569Gly). This variant is present in population databases (rs372671883, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with KCNQ3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1313762). 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) performed at Invitae indicates that this missense variant is expected to disrupt KCNQ3 protein function with a positive predictive value of 80%. 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.
Institute of Human Genetics, University of Goettingen RCV003320845 SCV004024564 uncertain significance Seizures, benign familial neonatal, 2 criteria provided, single submitter clinical testing

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