Submissions for variant NM_004519.4(KCNQ3):c.1720C>T (p.Pro574Ser)

dbSNP: rs74582884

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000081107	SCV000113015	benign	not specified	2014-06-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000081107	SCV000247669	likely benign	not specified	2016-03-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000384756	SCV000471913	likely benign	Benign Neonatal Epilepsy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000661926	SCV000471914	benign	Seizures, benign familial neonatal, 2	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV001529220	SCV000513384	benign	not provided	2018-05-25	criteria provided, single submitter	clinical testing	Published functional studies demonstrate no damaging effect, specifically, voltage clamp analysis revealed no significant reduction in potassium current as compared to wildtype (Neubauer et al., 2008); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28351718, 20981092, 18625963, 19344764, 23596459, 25784856, 28488083, 27875746, 29948376)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000290815	SCV000555735	likely benign	Benign neonatal seizures	2024-01-28	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000661926	SCV000784250	likely benign	Seizures, benign familial neonatal, 2	2018-03-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002316199	SCV000849590	benign	Inborn genetic diseases	2018-12-29	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Mendelics	RCV000661926	SCV001137708	benign	Seizures, benign familial neonatal, 2	2019-05-28	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Strasbourg University Hospital	RCV001257744	SCV001434556	likely benign	Intellectual disability	2020-04-20	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001529220	SCV004163236	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	KCNQ3: PM5, BS2
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000661926	SCV004564116	benign	Seizures, benign familial neonatal, 2	2023-11-07	criteria provided, single submitter	clinical testing
GeneReviews	RCV000661926	SCV000041085	not provided	Seizures, benign familial neonatal, 2		no assertion provided	literature only	Allele is present at 0.3% in non-Finnish Europeans and 0.2% in Latinos (gnomAD). Overrepresented (p=0.008) in idiopathic generalized epilepsies (8/455 persons). Detected in other complex phenotypes; in 4 persons with rolandic epilepsy and in 1 with rolandic epilepsy and moderate psychomotor delay; in 3 persons with autism spectrum disorders and no additional neurologic features
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529220	SCV001742306	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001529220	SCV001926256	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001529220	SCV001968012	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003934846	SCV004756088	likely benign	KCNQ3-related disorder	2019-10-11	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).