ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.994A>G (p.Arg332Gly) (rs1555869758)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558218 SCV000634082 likely pathogenic Early infantile epileptic encephalopathy 2017-04-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 332 of the KCNQ2 protein (p.Arg332Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a KCNQ2-related disease. Family studies have indicated that this variant was not present in the parents of an individual with generalized epilepsy , which suggests that it was de novo in that affected individual (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change that has been shown to arise de novo in an affected individual. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ambry Genetics RCV000622400 SCV000741905 likely pathogenic Inborn genetic diseases 2017-02-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: LIKELY POSITIVE: Relevant Alteration(s) Detected
Ambry Genetics RCV000720422 SCV000851299 likely pathogenic Seizures 2016-11-17 criteria provided, single submitter clinical testing Insufficient evidence;Confirmed de novo alteration in the setting of a new disease (appropriate phenotype) in the family;Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species

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