ClinVar Miner

Submissions for variant NM_004519.4(KCNQ3):c.688C>T (p.Arg230Cys) (rs796052676)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187968 SCV000241571 pathogenic not provided 2018-05-18 criteria provided, single submitter clinical testing The R230C pathogenic variant in the KCNQ3 gene has been reported previously using alternate nomenclature (R110C) as a de novo variant in an individual reported to have severe intellectual disability, autism, aggressive behavior, and EEG abnormalities but no evidence of seizures (Rauch et al., 2012). R230C has also been reported as a de novo variant in an individual with Lennox-Gastaut syndrome (Allen et al., 2013). This variant is not observed in large population cohorts (Lek et al., 2016). The R230C 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 a conserved position predicted to be located within transmembrane segment S4 (the voltage sensor) of the KCNQ3 protein. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Functional studies of R230C indicate that it causes a gain-of-function stabilization of the ion channel's activated state (Miceli et al., 2015). Therefore, we interpret R230C as a pathogenic variant.
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000210407 SCV000258451 likely pathogenic Benign familial neonatal seizures 2 2015-09-09 criteria provided, single submitter research This study shows that diverse genetic causes underlie CVI.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000210407 SCV000584064 pathogenic Benign familial neonatal seizures 2 2017-06-08 criteria provided, single submitter research
Fulgent Genetics,Fulgent Genetics RCV000210407 SCV000611276 pathogenic Benign familial neonatal seizures 2 2017-05-18 criteria provided, single submitter clinical testing
Genetics Laboratory - UDIAT Centre Diagnòstic, Hospital Universitari Parc Tauli RCV000824686 SCV000930699 pathogenic Severe neurodevelopmental delay 2019-07-10 criteria provided, single submitter clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000824975 SCV000966152 pathogenic Seizures, benign familial infantile, 5 2018-08-28 criteria provided, single submitter clinical testing
Invitae RCV001042557 SCV001206243 pathogenic Benign familial neonatal seizures 2019-11-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 230 of the KCNQ3 protein (p.Arg230Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in several individuals affected with early-onset epileptic encephalopathy (PMID: 23020937, 23934111) and has been reported in several additional individuals with neurodevelopmental disorders (PMID: 28135719, 26350515, 28628100, 29655203). This variant is also known as p.Arg110Cys, g.133192493G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 205963). This variant has been reported to affect KCNQ3 protein function (PMID:25740509, 30578330). For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001197919 SCV001368702 likely pathogenic Global developmental delay; Sleep disturbance; Hypoplasia of the corpus callosum; Intellectual disability; Periventricular leukomalacia 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PP3. This variant was detected in heterozygous state.
GenomeConnect, ClinGen RCV001249311 SCV001423274 not provided Intellectual disability; Benign familial neonatal seizures; Lennox-Gastaut syndrome no assertion provided phenotyping only Variant interpretted as Pathogenic and reported on 10-08-2018 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.