ClinVar Miner

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

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Total submissions: 6
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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

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