Submissions for variant NM_172107.4(KCNQ2):c.1657C>T (p.Arg553Trp)

dbSNP: rs759584387

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187912	SCV000241514	pathogenic	not provided	2022-08-06	criteria provided, single submitter	clinical testing	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; This variant is associated with the following publications: (PMID: 23621294, 27535030, 29655203, 31302675, 31780880, 31552204, 32860008, 32117026, 32863083, 33659638, 35693682, 27602407)
NeuroMeGen, Hospital Clinico Santiago de Compostela	RCV000203596	SCV000258979	pathogenic	Seizures, benign familial neonatal, 1		criteria provided, single submitter	clinical testing
Invitae	RCV000706752	SCV000835821	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2024-01-17	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 553 of the KCNQ2 protein (p.Arg553Trp). This variant is present in population databases (rs759584387, gnomAD 0.0009%). This missense change has been observed in individual(s) with early infantile epileptic encephalopathy and benign neonatal seizures (PMID: 23621294, 27535030). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 205913). 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. This variant disrupts the p.Arg553 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23621294). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Mendelics	RCV000203596	SCV001141270	pathogenic	Seizures, benign familial neonatal, 1	2022-09-20	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000187912	SCV001247375	pathogenic	not provided	2021-08-01	criteria provided, single submitter	clinical testing
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV001251207	SCV001424580	pathogenic	Seizure	2020-07-24	criteria provided, single submitter	clinical testing	Absent from gnomAD. Predicted deleterious. Several publications.
Centogene AG - the Rare Disease Company	RCV000678185	SCV001426559	pathogenic	Developmental and epileptic encephalopathy, 7		criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000187912	SCV002023226	pathogenic	not provided	2019-12-24	criteria provided, single submitter	clinical testing
GeneReviews	RCV000678185	SCV000484634	not provided	Developmental and epileptic encephalopathy, 7		no assertion provided	literature only	EE (epileptic encephalopathy)
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000187912	SCV001931826	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000187912	SCV001951274	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Center of Excellence for Medical Genomics, Chulalongkorn University	RCV000678185	SCV002564404	pathogenic	Developmental and epileptic encephalopathy, 7	2022-08-19	no assertion criteria provided	research
Center of Excellence for Medical Genomics, Chulalongkorn University	RCV000203596	SCV002570024	pathogenic	Seizures, benign familial neonatal, 1	2002-09-08	no assertion criteria provided	research