Submissions for variant NM_000218.3(KCNQ1):c.1343C>G (p.Pro448Arg)

dbSNP: rs12720449

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000171758	SCV000055279	likely benign	Long QT syndrome	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155365	SCV000205052	benign	not specified	2012-05-07	criteria provided, single submitter	clinical testing	Pro448Arg in Exon 10 of KCNQ1: This variant is not expected to have clinical sig nificance because it has been identified in 5.8% (7/120) of chromosomes from a p opulation in the dbSNP database (http://www.ncbi.nlm.nih.gov/projects/SNP; rs127 20449).
Ambry Genetics	RCV000252693	SCV000318865	benign	Cardiovascular phenotype	2015-04-21	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.
Illumina Laboratory Services, Illumina	RCV001093977	SCV000370295	benign	Long QT syndrome 1	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000171758	SCV000555794	benign	Long QT syndrome	2024-02-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000057578	SCV000604063	benign	not provided	2019-10-02	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000057578	SCV000609938	likely benign	not provided	2017-08-08	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000155365	SCV000861670	benign	not specified	2018-06-20	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001841662	SCV000910692	benign	Cardiac arrhythmia	2018-03-19	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001102906	SCV001259606	benign	Atrial fibrillation, familial, 3	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.
Illumina Laboratory Services, Illumina	RCV001102907	SCV001259607	benign	Jervell and Lange-Nielsen syndrome 1	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.
Illumina Laboratory Services, Illumina	RCV001102908	SCV001259608	benign	Short QT syndrome type 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	RCV000057578	SCV001846493	benign	not provided	2020-03-11	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 31043699, 28988457, 27153395, 10973849, 22479571, 15242738, 24618965, 11997281, 15051636, 22949429, 26846766)
Breakthrough Genomics, Breakthrough Genomics	RCV000057578	SCV005223175	likely benign	not provided		criteria provided, single submitter	not provided
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000057578	SCV000089097	not provided	not provided		no assertion provided	literature only	This variant has been reported in the following publications (PMID:10973849;PMID:11997281;PMID:14661677;PMID:14731347;PMID:15051636;PMID:15242738;PMID:16155735;PMID:16487223;PMID:17016049;PMID:17210839;PMID:17597962;PMID:19841300).
Clinical Genetics, Academic Medical Center	RCV000155365	SCV001925999	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000155365	SCV001932268	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000155365	SCV001954545	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000057578	SCV002036807	likely benign	not provided		no assertion criteria provided	clinical testing