ClinVar Miner

Submissions for variant NM_004519.4(KCNQ3):c.988C>T (p.Arg330Cys)

dbSNP: rs118192251
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000462450 SCV000543210 pathogenic Benign neonatal seizures 2023-05-15 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KCNQ3 protein function. ClinVar contains an entry for this variant (Variation ID: 21417). This missense change has been observed in individuals with benign familial neonatal seizures (PMID: 18249525, 23146207). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 330 of the KCNQ3 protein (p.Arg330Cys).
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000020602 SCV000743523 pathogenic Seizures, benign familial neonatal, 2 2014-10-08 criteria provided, single submitter clinical testing
3billion RCV000020602 SCV002012197 likely pathogenic Seizures, benign familial neonatal, 2 2021-10-02 criteria provided, single submitter clinical testing Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (PMID: 23146207, PS1). It is not observed in the gnomAD v2.1.1 dataset (PM2). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.973, 3Cnet: 0.981, PP3). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
GeneDx RCV003233074 SCV003931034 pathogenic not provided 2022-12-05 criteria provided, single submitter clinical testing Published functional studies demonstrate abnormal channel function (Miceli et al., 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23146207, 16883520, 28717674, 35627257, 34474328, 18249525, 25524373, 34136434)
GeneReviews RCV000020602 SCV000041091 not provided Seizures, benign familial neonatal, 2 no assertion provided literature only Same variant detected in 2 unrelated families
OMIM RCV000020602 SCV000121585 pathogenic Seizures, benign familial neonatal, 2 2013-05-01 no assertion criteria provided literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000020602 SCV000734592 pathogenic Seizures, benign familial neonatal, 2 no assertion criteria provided clinical testing

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