Submissions for variant NM_172107.4(KCNQ2):c.1639C>T (p.Arg547Trp)

dbSNP: rs796052650

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187911	SCV000241513	likely pathogenic	not provided	2022-04-22	criteria provided, single submitter	clinical testing	Identified in unrelated patients with clinical features consistent with a KCNQ2-related disorder referred for genetic testing at GeneDx and in patients with neonatal-onset seizures in the published literature (Zara et al., 2013; Panjan et al., 2021; Amore et al., 2022); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28717674, 29655203, 34474328, 35401395, 29455050, 23360469, 27602407)
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000187911	SCV000511083	likely pathogenic	not provided	2016-09-02	criteria provided, single submitter	clinical testing
Invitae	RCV000551309	SCV000634050	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2023-11-02	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 547 of the KCNQ2 protein (p.Arg547Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with benign familial neonatal-infantile seizures (PMID: 23360469, 29655203; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 205912). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000187911	SCV001247376	pathogenic	not provided	2017-11-01	criteria provided, single submitter	clinical testing
GeneReviews	RCV000678183	SCV000484630	not provided	Seizures, benign familial neonatal, 1		no assertion provided	literature only	BFNE (benign familial neonatal epilepsy)