Submissions for variant NM_000218.3(KCNQ1):c.513C>A (p.Tyr171Ter)

dbSNP: rs139042529

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000617940	SCV000738002	pathogenic	Cardiovascular phenotype	2017-06-08	criteria provided, single submitter	clinical testing	The p.Y171* pathogenic mutation (also known as c.513C>A), located in coding exon 3 of the KCNQ1 gene, results from a C to A substitution at nucleotide position 513. This changes the amino acid from a tyrosine to a stop codon within coding exon 3. This alteration has been reported in a sudden cardiac arrest/death cohort (Li MH et al. Human Genomics, 2015 9:15). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000814153	SCV000954554	pathogenic	Long QT syndrome	2024-03-26	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr171*) in the KCNQ1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNQ1 are known to be pathogenic (PMID: 9323054, 19862833). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Jervell and Lange-Nielsen syndrome and/or long QT syndrome (PMID: 11216980, 12051962, 14678125, 26187847). ClinVar contains an entry for this variant (Variation ID: 265209). For these reasons, this variant has been classified as Pathogenic.
MGZ Medical Genetics Center	RCV000477871	SCV002580040	likely pathogenic	Long QT syndrome 1	2022-06-24	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV003591726	SCV004358372	pathogenic	Cardiac arrhythmia	2023-06-21	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 3 of the KCNQ1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. A functional study has shown that this variant results in undetectable expression of KCNQ1 in RNA and protein levels and no functional potassium current in transfected cells (PMID: 33504163). This variant has been reported in at least three unrelated individuals affected with long QT syndrome (PMID: 14678125, 32893267), in an individual affected with sudden cardiac arrest or death (PMID: 26187847), and in an asymptomatic individual (PMID: 33504163). A different nucleotide change (c.513C>G) leading to the same nonsense variant has been determined to be pathogenic (ClinVar variation ID 53056). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of KCNQ1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
All of Us Research Program, National Institutes of Health	RCV000814153	SCV004825203	pathogenic	Long QT syndrome	2024-01-08	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 3 of the KCNQ1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. A functional study has shown that this variant results in undetectable expression of KCNQ1 in RNA and protein levels and no functional potassium current in transfected cells (PMID: 33504163). This variant has been reported in at least three unrelated individuals affected with long QT syndrome (PMID: 14678125, 32893267), in an individual affected with sudden cardiac arrest or death (PMID: 26187847), and in an asymptomatic individual (PMID: 33504163). A different nucleotide change (c.513C>G) leading to the same nonsense variant has been determined to be pathogenic (ClinVar variation ID 53056). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of KCNQ1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Department of Human Genetics, Hannover Medical School	RCV000477871	SCV005894816	pathogenic	Long QT syndrome 1	2025-03-21	criteria provided, single submitter	clinical testing	ACMG: PVS1, PM2_Supporting, PP4_Moderate
Division of Human Genetics, Children's Hospital of Philadelphia	RCV000477871	SCV000536844	pathogenic	Long QT syndrome 1	2016-02-25	no assertion criteria provided	research