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NM_181798.1(KCNQ1):c.40G>A (p.Val14Met)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
7 (Most recent: Oct 15, 2021)
Last evaluated:
Jan 17, 2020
Accession:
VCV000067072.6
Variation ID:
67072
Description:
single nucleotide variant
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NM_181798.1(KCNQ1):c.40G>A (p.Val14Met)

Allele ID
77968
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
11p15.5
Genomic location
11: 2527962 (GRCh38) GRCh38 UCSC
11: 2549192 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_287:g.87972G>A
NC_000011.10:g.2527962G>A
NC_000011.9:g.2549192G>A
... more HGVS
Protein change
V141M, V14M
Other names
-
Canonical SPDI
NC_000011.10:2527961:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA007045
OMIM: 607542.0045
dbSNP: rs199472687
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 1 criteria provided, single submitter Mar 7, 2018 RCV000468931.4
Pathogenic 3 criteria provided, single submitter Jan 17, 2020 RCV000494365.3
Pathogenic 1 criteria provided, single submitter Dec 2, 2016 RCV000621525.1
Pathogenic 1 no assertion criteria provided Dec 1, 2005 RCV000417071.1
not provided 1 no assertion provided - RCV000057674.3
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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
1161 1427

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Mar 07, 2018)
criteria provided, single submitter
Method: clinical testing
Long QT syndrome
Allele origin: germline
Invitae
Accession: SCV000543288.4
Submitted: (Aug 29, 2018)
Evidence details
Publications
PubMed (8)
Comment:
This sequence change replaces valine with methionine at codon 141 of the KCNQ1 protein (p.Val141Met). The valine residue is highly conserved and there is a … (more)
Pathogenic
(Dec 02, 2016)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000737832.3
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (5)
Comment:
The p.V141M pathogenic mutation (also known as c.421G>A), located in coding exon 2 of the KCNQ1 gene, results from a G to A substitution at … (more)
Pathogenic
(Jan 17, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000582623.3
Submitted: (Sep 25, 2021)
Evidence details
Comment:
Reported in ClinVar as a pathogenic variant (ClinVar Variant ID# 67072; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); … (more)
Pathogenic
(Dec 01, 2005)
no assertion criteria provided
Method: literature only
SHORT QT SYNDROME 2
Allele origin: germline
OMIM
Accession: SCV000494620.1
Submitted: (Feb 09, 2017)
Evidence details
Publications
PubMed (2)
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Clinical Genetics,Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001979196.1
Submitted: (Oct 15, 2021)
Evidence details
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Human Genetics - Radboudumc,Radboudumc
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001979332.1
Submitted: (Oct 15, 2021)
Evidence details
not provided
(-)
no assertion provided
Method: literature only
Atrial fibrillation
Allele origin: germline
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust
Accession: SCV000089193.3
Submitted: (Sep 22, 2016)
Evidence details
Publications
PubMed (5)
Comment:
This variant has been reported as associated with Atrial fibrillation in the following publications (PMID:16109388;PMID:18599533;PMID:22250012;PMID:17999538). This is a literature report, and does not necessarily reflect … (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
Genotype-dependent differences in age of manifestation and arrhythmia complications in short QT syndrome. Harrell DT International journal of cardiology 2015 PMID: 25974115
UniProt: a hub for protein information. UniProt Consortium. Nucleic acids research 2015 PMID: 25348405
Short QT syndrome manifesting with neonatal atrial fibrillation and bradycardia. Villafañe J Cardiology 2014 PMID: 24818999
Selective targeting of gain-of-function KCNQ1 mutations predisposing to atrial fibrillation. Campbell CM Circulation. Arrhythmia and electrophysiology 2013 PMID: 24006450
Long-term follow-up of a pediatric cohort with short QT syndrome. Villafañe J Journal of the American College of Cardiology 2013 PMID: 23375927
Paralogous annotation of disease-causing variants in long QT syndrome genes. Ware JS Human mutation 2012 PMID: 22581653
Characterization of KCNQ1 atrial fibrillation mutations reveals distinct dependence on KCNE1. Chan PJ The Journal of general physiology 2012 PMID: 22250012
Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Kapa S Circulation 2009 PMID: 19841300
Mechanisms by which atrial fibrillation-associated mutations in the S1 domain of KCNQ1 slow deactivation of IKs channels. Restier L The Journal of physiology 2008 PMID: 18599533
Structural models for the KCNQ1 voltage-gated potassium channel. Smith JA Biochemistry 2007 PMID: 17999538
De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero. Hong K Cardiovascular research 2005 PMID: 16109388

Text-mined citations for rs199472687...

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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 Oct 16, 2021