ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.380A>G (p.Tyr127Cys)

dbSNP: rs796052617
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187852 SCV000241452 pathogenic not provided 2020-12-10 criteria provided, single submitter clinical testing Electrophysiology assays were performed using CHO cells transfected with Y127C and R207W variant cDNA constructs, and reduced potentiation on the outward currents was observed, however, the variants were not tested individually (Zheng et al., 2015); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 25735002)
Invitae RCV001232372 SCV001404928 likely pathogenic Early infantile epileptic encephalopathy with suppression bursts 2019-11-14 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with infantile onset epilepsy (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 205863). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 127 of the KCNQ2 protein (p.Tyr127Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine.
Fulgent Genetics, Fulgent Genetics RCV002478657 SCV002801801 likely pathogenic Seizures, benign familial neonatal, 1; Developmental and epileptic encephalopathy, 7 2021-07-15 criteria provided, single submitter clinical testing

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