Submissions for variant NM_000218.3(KCNQ1):c.1394-14C>T

gnomAD frequency: 0.01027  dbSNP: rs28730758

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035340	SCV000058988	benign	not specified	2012-04-30	criteria provided, single submitter	clinical testing	1394-14C>T in Intron 10 of KCNQ1: This variant is not expected to have clinical significance because it has been identified in 1.5% (106/7020) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs28730758).
PreventionGenetics, part of Exact Sciences	RCV000035340	SCV000303043	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000358014	SCV000370326	benign	Long QT syndrome 1	2018-01-13	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	RCV000265135	SCV000370327	likely benign	Atrial fibrillation, familial, 3	2018-01-13	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000317977	SCV000370328	benign	Jervell and Lange-Nielsen syndrome 1	2018-01-13	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	RCV000374940	SCV000370329	benign	Short QT syndrome type 2	2018-01-13	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	RCV000259662	SCV000370330	likely benign	Congenital long QT syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001841556	SCV000902640	benign	Cardiac arrhythmia	2018-03-19	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001636619	SCV001159495	benign	not provided	2023-11-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000035340	SCV001361862	benign	not specified	2019-08-12	criteria provided, single submitter	clinical testing	Variant summary: KCNQ1 c.1394-14C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.011 in 251268 control chromosomes, predominantly at a frequency of 0.044 within the East Asian subpopulation in the gnomAD database, including 21 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 440-folds over the estimated maximal expected allele frequency for a pathogenic variant in KCNQ1 causing Arrhythmia phenotype (0.0001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. Two ClinVar submissions (evaluation after 2014) cite the variant once as benign and once as likely benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV001636619	SCV001851669	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Invitae	RCV002054558	SCV002369014	benign	Long QT syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000035340	SCV001932810	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000035340	SCV001956779	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035340	SCV001979130	benign	not specified		no assertion criteria provided	clinical testing