ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.1057C>T (p.Arg353Cys)

dbSNP: rs118192218
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187895 SCV000241497 pathogenic not provided 2020-12-23 criteria provided, single submitter clinical testing The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 29726930)
Athena Diagnostics Inc RCV000517065 SCV000613874 uncertain significance not specified 2016-09-29 criteria provided, single submitter clinical testing
Invitae RCV000694219 SCV000822653 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2022-05-21 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg353 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25959266). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 KCNQ2 protein function. ClinVar contains an entry for this variant (Variation ID: 205898). This missense change has been observed in individual(s) with clinical features of benign familial neonatal seizures (PMID: 29726930). In at least one individual the variant was observed to be de novo. 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 353 of the KCNQ2 protein (p.Arg353Cys).
Duke University Health System Sequencing Clinic, Duke University Health System RCV003223393 SCV003919016 likely pathogenic Seizures, benign familial neonatal, 1 2023-04-20 criteria provided, single submitter research

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