Submissions for variant NM_000218.3(KCNQ1):c.513C>T (p.Tyr171=)

dbSNP: rs139042529

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155132	SCV000204818	likely benign	not specified	2012-04-30	criteria provided, single submitter	clinical testing	p.Tyr171Tyr in exon 3 of KCNQ1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 0.2% (11/7020) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs139042529).
Ambry Genetics	RCV000247674	SCV000319196	likely benign	Cardiovascular phenotype	2015-05-13	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.
Illumina Laboratory Services, Illumina	RCV001094042	SCV000370245	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). 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	RCV000268526	SCV000370247	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	RCV000323618	SCV000370248	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.
Illumina Laboratory Services, Illumina	RCV000378309	SCV000370249	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000326765	SCV000555800	benign	Long QT syndrome	2024-01-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590559	SCV000695989	benign	not provided	2017-11-22	criteria provided, single submitter	clinical testing	Variant summary: The KCNQ1 c.513C>T (p.Tyr171Tyr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE site of SRp55. However, these predictions have yet to be confirmed by functional studies. This variant was found in 240/275760 control chromosomes (gnomAD) at a frequency of 0.0008703, which is approximately 9 times the estimated maximal expected allele frequency of a pathogenic KCNQ1 variant (0.0001), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as benign.
Color Diagnostics, LLC DBA Color Health	RCV001842485	SCV000911144	benign	Cardiac arrhythmia	2018-04-26	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000590559	SCV001748267	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	KCNQ1: BP4, BP7
GeneDx	RCV000590559	SCV001940534	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004534985	SCV004752284	likely benign	KCNQ1-related disorder	2019-04-15	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).