ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.2173C>T (p.Arg725Cys)

gnomAD frequency: 0.00004  dbSNP: rs768284828
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000529314 SCV000634060 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2024-10-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 725 of the KCNQ2 protein (p.Arg725Cys). This variant is present in population databases (rs768284828, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with KCNQ2-related conditions. ClinVar contains an entry for this variant (Variation ID: 461414). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt KCNQ2 protein function with a positive predictive value of 95%. 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.
GeneDx RCV001564307 SCV001787454 likely benign not provided 2021-03-31 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV003338650 SCV004048361 uncertain significance Developmental and epileptic encephalopathy, 7 criteria provided, single submitter clinical testing The missense variant c.2173C>T (p.Arg725Cys) in KCNQ2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency (0.003%) in the gnomAD and novel in 1000 genome database. The amino acid Arginine at position 725 is changed to a Cysteine changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. For these reasons, this variant has been classified as Uncertain Significance.

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