ClinVar Miner

Submissions for variant NM_004519.4(KCNQ3):c.2462A>G (p.Asn821Ser) (rs118192254)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723967 SCV000226291 uncertain significance not provided 2014-06-06 criteria provided, single submitter clinical testing
GeneDx RCV000187958 SCV000241561 likely benign not specified 2017-10-19 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Clinical Services Laboratory,Illumina RCV000327599 SCV000471883 likely benign Benign Neonatal Epilepsy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000368463 SCV000471884 likely benign Benign familial neonatal seizures 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000368463 SCV000828546 uncertain significance Benign familial neonatal seizures 2019-12-16 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 821 of the KCNQ3 protein (p.Asn821Ser). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs118192254, ExAC 0.07%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with benign familial neonatal convulsion (PMID: 16235065). However this variant was inherited from the unaffected father of the proband. Furthermore, a variant in KCNQ2 was also found in the proband, which segregated with disease in maternal relatives. This variant is also known as c.2687A>G in the literature. ClinVar contains an entry for this variant (Variation ID: 21412). Experimental studies have shown that protein products with this missense change was indistinguishable from wild-type in biochemical and electrophysiological features (PMID: 16235065). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Ambry Genetics RCV000717890 SCV000848750 benign Seizures 2018-05-30 criteria provided, single submitter clinical testing Intact protein function observed in appropriate functional assay(s);Other data supporting benign classification;In silico models in agreement (benign)
GeneReviews RCV000678048 SCV000041086 pathogenic Benign familial neonatal seizures 2 2010-04-27 no assertion criteria provided curation Converted during submission to Pathogenic.

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