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NM_000218.3(KCNQ1):c.520C>T (p.Arg174Cys)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6 (Most recent: Sep 29, 2021)
Last evaluated:
Feb 4, 2021
Accession:
VCV000053058.6
Variation ID:
53058
Description:
single nucleotide variant
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NM_000218.3(KCNQ1):c.520C>T (p.Arg174Cys)

Allele ID
67726
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
11p15.5
Genomic location
11: 2570670 (GRCh38) GRCh38 UCSC
11: 2591900 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P51787:p.Arg174Cys
NC_000011.9:g.2591900C>T
NM_000218.2:c.520C>T NP_000209.2:p.Arg174Cys missense
... more HGVS
Protein change
R174C, R47C
Other names
p.R174C:CGC>TGC
Canonical SPDI
NC_000011.10:2570669:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Links
ClinGen: CA007321
UniProtKB: P51787#VAR_001517
dbSNP: rs199472696
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, single submitter Jun 28, 2020 RCV000046072.9
Pathogenic 1 criteria provided, single submitter Feb 4, 2021 RCV000182078.5
Pathogenic 1 criteria provided, single submitter Feb 1, 2016 RCV000587627.1
Likely pathogenic 1 criteria provided, single submitter Nov 4, 2018 RCV001184215.1
not provided 1 no assertion provided - RCV000057689.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
KCNQ1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh38
GRCh37
1168 1436

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Jun 28, 2020)
criteria provided, single submitter
Method: clinical testing
Long QT syndrome
Allele origin: germline
Invitae
Accession: SCV000074085.8
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (9)
Comment:
This sequence change replaces arginine with cysteine at codon 174 of the KCNQ1 protein (p.Arg174Cys). The arginine residue is highly conserved and there is a … (more)
Pathogenic
(Feb 04, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000234381.14
Submitted: (Sep 29, 2021)
Evidence details
Comment:
Reported as pathogenic in ClinVar by other clinical laboratories (ClinVar Variant ID# 53058; Landrum et al., 2016); Not observed at a significant frequency in large … (more)
Pathogenic
(Feb 01, 2016)
criteria provided, single submitter
Method: clinical testing
Long QT syndrome 1
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695990.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (6)
Comment:
Variant summary: The c.520C>T (p.R174C) in KCNQ1 gene is a missense variant that involves a conserved nucleotide and 5/5 in silico tools predict deleterious outcome. … (more)
Likely pathogenic
(Nov 04, 2018)
criteria provided, single submitter
Method: clinical testing
Arrhythmia
Allele origin: germline
Color Health, Inc
Accession: SCV001350155.1
Submitted: (May 19, 2020)
Comment:
This missense variant is located in the cytoplasmic linker between transmembrane domains S2 and S3 of the KCNQ1 protein. Computational prediction tools and conservation analyses … (more)
Evidence details
Pathogenic
(Sep 10, 2015)
no assertion criteria provided
Method: clinical testing
Long QT syndrome
Allele origin: germline
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital
Accession: SCV000804994.1
Submitted: (Jul 17, 2018)
Evidence details
not provided
(-)
no assertion provided
Method: literature only
Congenital long QT syndrome
Allele origin: germline
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust
Accession: SCV000089208.3
Submitted: (Sep 22, 2016)
Evidence details
Publications
PubMed (6)
Comment:
This variant has been reported as associated with Long QT syndrome in the following publications (PMID:9386136;PMID:11668638;PMID:15840476;PMID:19716085;PMID:19934648). This is a literature report, and does not necessarily … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Prevalence and potential genetic determinants of sensorineural deafness in KCNQ1 homozygosity and compound heterozygosity. Giudicessi JR Circulation. Cardiovascular genetics 2013 PMID: 23392653
Genotype- and Sex-Specific QT-RR Relationship in the Type-1 Long-QT Syndrome. Couderc JP Journal of the American Heart Association 2012 PMID: 23130128
Paralogous annotation of disease-causing variants in long QT syndrome genes. Ware JS Human mutation 2012 PMID: 22581653
PKA and PKC partially rescue long QT type 1 phenotype by restoring channel-PIP2 interactions. Matavel A Channels (Austin, Tex.) 2010 PMID: 19934648
Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Kapplinger JD Heart rhythm 2009 PMID: 19716085
Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Tester DJ Heart rhythm 2005 PMID: 15840476
Automated mutation screening using dideoxy fingerprinting and capillary array electrophoresis. Larsen LA Human mutation 2001 PMID: 11668638
Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Splawski I Circulation 2000 PMID: 10973849
KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome. Donger C Circulation 1997 PMID: 9386136
Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias. Chouabe C The EMBO journal 1997 PMID: 9312006

Text-mined citations for rs199472696...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 20, 2021