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NM_181798.1(KCNQ1):c.1175G>A (p.Arg392His)

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Interpretation:
Conflicting interpretations of pathogenicity​

Benign(1);Likely benign(1);Uncertain significance(6)

Review status:
criteria provided, conflicting interpretations
Submissions:
9 (Most recent: Jan 7, 2021)
Last evaluated:
Jun 4, 2020
Accession:
VCV000067038.7
Variation ID:
67038
Description:
single nucleotide variant
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NM_181798.1(KCNQ1):c.1175G>A (p.Arg392His)

Allele ID
77934
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
11p15.5
Genomic location
11: 2768885 (GRCh38) GRCh38 UCSC
11: 2790115 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_287t1:c.1556G>A LRG_287p1:p.Arg519His
LRG_287:g.328895G>A
LRG_287t2:c.1175G>A LRG_287p2:p.Arg392His
... more HGVS
Protein change
R519H, R392H
Other names
-
Canonical SPDI
NC_000011.10:2768884:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00002
Exome Aggregation Consortium (ExAC) 0.00003
Links
ClinGen: CA005923
dbSNP: rs199472788
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, single submitter Aug 24, 2018 RCV000057596.3
Uncertain significance 1 criteria provided, single submitter Jun 4, 2020 RCV000543065.5
Uncertain significance 1 criteria provided, single submitter Aug 24, 2017 RCV001104917.1
Uncertain significance 1 criteria provided, single submitter Aug 24, 2017 RCV001106072.1
Uncertain significance 1 criteria provided, single submitter Sep 10, 2019 RCV001188386.1
Likely benign 1 criteria provided, single submitter Aug 24, 2017 RCV001104916.1
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations May 28, 2019 RCV000988473.2
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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
Uncertain significance
(Aug 24, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000863169.1
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Benign
(May 28, 2019)
criteria provided, single submitter
Method: clinical testing
Long QT syndrome 1
Allele origin: unknown
Mendelics
Accession: SCV001138206.1
Submitted: (Oct 22, 2019)
Evidence details
Likely benign
(Aug 24, 2017)
criteria provided, single submitter
Method: clinical testing
Short QT syndrome 2
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001261822.1
Submitted: (Feb 20, 2020)
Evidence details
Publications
PubMed (6)
Comment:
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, … (more)
Uncertain significance
(Aug 24, 2017)
criteria provided, single submitter
Method: clinical testing
Atrial fibrillation, familial, 3
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001263103.1
Submitted: (Feb 20, 2020)
Evidence details
Publications
PubMed (6)
Comment:
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, … (more)
Uncertain significance
(Aug 24, 2017)
criteria provided, single submitter
Method: clinical testing
Long QT syndrome 1
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001263104.1
Submitted: (Feb 20, 2020)
Evidence details
Publications
PubMed (6)
Comment:
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, … (more)
Uncertain significance
(Aug 24, 2017)
criteria provided, single submitter
Method: clinical testing
Jervell and Lange-Nielsen syndrome 1
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001261823.1
Submitted: (Feb 20, 2020)
Evidence details
Publications
PubMed (6)
Comment:
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, … (more)
Uncertain significance
(Sep 10, 2019)
criteria provided, single submitter
Method: clinical testing
Arrhythmia
Allele origin: germline
Color Health, Inc
Accession: SCV001355442.1
Submitted: (May 19, 2020)
Comment:
This missense variant replaces arginine with histidine at codon 519 of the KCNQ1 protein. Computational prediction tool suggests that this variant may have deleterious impact … (more)
Evidence details
Uncertain significance
(Jun 04, 2020)
criteria provided, single submitter
Method: clinical testing
Long QT syndrome
Allele origin: germline
Invitae
Accession: SCV000627378.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change replaces arginine with histidine at codon 519 of the KCNQ1 protein (p.Arg519His). The arginine residue is highly conserved and there is a … (more)
not provided
(-)
no assertion provided
Method: literature only
not provided
Allele origin: germline
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust
Accession: SCV000089115.3
Submitted: (Sep 22, 2016)
Evidence details
Publications
PubMed (3)
Comment:
This variant has been reported in the following publications (PMID:14661677;PMID:19841300).

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
A Common Mutation of Long QT Syndrome Type 1 in Japan. Itoh H Circulation journal : official journal of the Japanese Circulation Society 2015 PMID: 26118460
UniProt: a hub for protein information. UniProt Consortium. Nucleic acids research 2015 PMID: 25348405
Tox-database.net: a curated resource for data describing chemical triggered in vitro cardiac ion channels inhibition. Polak S BMC pharmacology & toxicology 2012 PMID: 22947121
Paralogous annotation of disease-causing variants in long QT syndrome genes. Ware JS Human mutation 2012 PMID: 22581653
Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Kapa S Circulation 2009 PMID: 19841300
The single nucleotide polymorphisms of I(Ks) potassium channel genes and their association with atrial fibrillation in a Chinese population. Zeng Z Cardiology 2007 PMID: 17016049
Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome. Ackerman MJ Mayo Clinic proceedings 2003 PMID: 14661677
Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients. Krinsley JS Mayo Clinic proceedings 2003 PMID: 14661676
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=KCNQ1 - - - -

Text-mined citations for rs199472788...

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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 08, 2021