ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.868G>T (p.Gly290Cys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV002468419 SCV002764233 pathogenic Developmental and epileptic encephalopathy, 7 2020-08-18 criteria provided, single submitter research A heterozygous de novo missense variation in exon 6 of the KCNQ2 gene that results in the amino acid substitution of Cysteine for Glycine at codon 290 was detected. The observed variant c.868G>T (p.Gly290Cys) has not been reported in the 1000 genomes and ExAC databases. The in silico prediction of the variant are possibly damaging by PolyPhen-2 (HumDiv) and damaging by SIFT, LRT and MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as pathogenic.
Neuberg Centre For Genomic Medicine, NCGM RCV002468419 SCV002820255 likely pathogenic Developmental and epileptic encephalopathy, 7 criteria provided, single submitter clinical testing The missense variant p.G290C in KCNQ2 (NM_172107.3) causes a change at the same amino acid residue as a previously established pathogenic variant (G290D). The p.G290C variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. There is a large physicochemical difference between glycine and cysteine, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. The gene KCNQ2 contains 114 pathogenic missense variants, indicating that missense variants are a common mechanism of disease in this gene. The p.G290C missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glycine residue at codon 290 of KCNQ2 is conserved in all mammalian species. The nucleotide c.868 in KCNQ2 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic.

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