Submissions for variant NM_000218.3(KCNQ1):c.1179G>T (p.Lys393Asn)

gnomAD frequency: 0.00053  dbSNP: rs12720457

Total submissions: 24

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000148543	SCV000050828	benign	Long QT syndrome	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154657	SCV000204333	likely benign	not specified	2017-07-20	criteria provided, single submitter	clinical testing	p.Lys393Asn in exon 9 of KCNQ1: This variant is not expected to have clinical si gnificance because it has been reported in the literature in both control and cl inical cohorts (Ackerman 2003, Moss 2007, Guidicessi 2012, Crotti 2013). In addi tion, this variant has been identified in 0.3% (27/10152) of Ashkenazi Jewish ch romosomes and 0.2% (52/30782) of South Asian chromosomes including 1 homozygote by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; db SNP rs12720457). Studies have shown that the p.Lys393Asn variant does not impact protein function (Shamgar 2006). Furthermore, the lysine (Lys) at amino acid po sition 393 is not conserved across species, including mammals. Of note, cat has an asparagine (Asn) at this position despite high nearby amino acid conservation . Additional computational analyses do not suggest a high likelihood of impact t o the protein. In summary, this variant is classified as likely benign based on the available data.
Eurofins Ntd Llc (ga)	RCV000057570	SCV000232929	uncertain significance	not provided	2015-01-16	criteria provided, single submitter	clinical testing
GeneDx	RCV000057570	SCV000234375	likely benign	not provided	2021-03-25	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 19862833, 25637381, 22949429, 23861362, 31337358, 16556865, 24400285, 23571586, 14661677, 17161064, 14678125, 17210839, 17470695, 19841300, 23396983, 24055113, 25854863, 28074886, 22677073, 30020974, 26970180, 29431662)
Illumina Laboratory Services, Illumina	RCV000394039	SCV000370275	likely benign	Congenital long QT syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000306809	SCV000370276	likely benign	Jervell and Lange-Nielsen syndrome 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001094051	SCV000370277	likely benign	Long QT syndrome 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000394030	SCV000370278	likely benign	Short QT syndrome type 2	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000305127	SCV000370279	likely benign	Atrial fibrillation, familial, 3	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000148543	SCV000555803	benign	Long QT syndrome	2024-01-29	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000057570	SCV000604064	likely benign	not provided	2023-09-14	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001841659	SCV000911310	likely benign	Cardiac arrhythmia	2018-03-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000154657	SCV000919556	likely benign	not specified	2017-10-16	criteria provided, single submitter	clinical testing	Variant summary: The KCNQ1 c.1179G>T (p.Lys393Asn) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 292/277174 control chromosomes, including 1 homozygous individual, predominantly observed in the Ashkenazi Jewish subpopulation at a frequency of 0.00266 (27/10152). This frequency is about 27 times the estimated maximal expected allele frequency of a pathogenic KCNQ1 variant (0.0001), suggesting this is likely a benign polymorphism found primarily in the populations of Ashkenazi Jewish origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as likely benign.
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852645	SCV000995350	benign	Cardiomyopathy	2017-08-30	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000057570	SCV001148156	likely benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	KCNQ1: BS2
Institute of Human Genetics, University of Leipzig Medical Center	RCV001094051	SCV001440824	likely benign	Long QT syndrome 1	2019-01-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002336208	SCV002637437	likely benign	Cardiovascular phenotype	2018-09-22	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Dept of Medical Biology, Uskudar University	RCV000148543	SCV004022028	uncertain significance	Long QT syndrome	2024-01-08	criteria provided, single submitter	research	Criteria: BS1
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000057570	SCV000089089	not provided	not provided		no assertion provided	literature only	This variant has been reported in the following publications (PMID:14661677;PMID:14678125;PMID:17161064;PMID:17210839;PMID:17470695;PMID:19841300;PMID:19862833).
CSER _CC_NCGL, University of Washington	RCV000148543	SCV000190256	likely benign	Long QT syndrome	2014-06-01	no assertion criteria provided	research
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000057570	SCV001799905	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000057570	SCV001926148	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000057570	SCV001953903	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000057570	SCV001974927	likely benign	not provided		no assertion criteria provided	clinical testing