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NM_000238.4(KCNH2):c.1781G>A (p.Gly594Asp)

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Interpretation:
Likely pathogenic​

Review status:
criteria provided, single submitter
Submissions:
2 (Most recent: Jan 7, 2021)
Last evaluated:
Jul 31, 2019
Accession:
VCV000067271.3
Variation ID:
67271
Description:
single nucleotide variant
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NM_000238.4(KCNH2):c.1781G>A (p.Gly594Asp)

Allele ID
78167
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
7q36.1
Genomic location
7: 150951612 (GRCh38) GRCh38 UCSC
7: 150648700 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000007.13:g.150648700C>T
NM_000238.3:c.1781G>A NP_000229.1:p.Gly594Asp missense
LRG_288t1:c.1781G>A LRG_288p1:p.Gly594Asp
... more HGVS
Protein change
G254D, G594D
Other names
-
Canonical SPDI
NC_000007.14:150951611:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Links
ClinGen: CA005466
UniProtKB: Q12809#VAR_074838
dbSNP: rs199472931
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 1 criteria provided, single submitter Jul 31, 2019 RCV001205698.1
not provided 1 no assertion provided - RCV000057987.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
KCNH2 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
2038 2109

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Jul 31, 2019)
criteria provided, single submitter
Method: clinical testing
Long QT syndrome
Allele origin: germline
Invitae
Accession: SCV001376967.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (6)
Comment:
This sequence change replaces glycine with aspartic acid at codon 594 of the KCNH2 protein (p.Gly594Asp). The glycine residue is moderately conserved and there is … (more)
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: SCV000089507.3
Submitted: (Sep 22, 2016)
Evidence details
Publications
PubMed (3)
Comment:
This variant has been reported as associated with Long QT syndrome in the following publications (PMID:19716085;PMID:19841300). 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
Large-scale mutational analysis of Kv11.1 reveals molecular insights into type 2 long QT syndrome. Anderson CL Nature communications 2014 PMID: 25417810
Vagal reflexes following an exercise stress test: a simple clinical tool for gene-specific risk stratification in the long QT syndrome. Crotti L Journal of the American College of Cardiology 2012 PMID: 23158531
Founder mutations characterise the mutation panorama in 200 Swedish index cases referred for Long QT syndrome genetic testing. Stattin EL BMC cardiovascular disorders 2012 PMID: 23098067
Phylogenetic and physicochemical analyses enhance the classification of rare nonsynonymous single nucleotide variants in type 1 and 2 long-QT syndrome. Giudicessi JR Circulation. Cardiovascular genetics 2012 PMID: 22949429
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
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
Long QT and Brugada syndrome gene mutations in New Zealand. Chung SK Heart rhythm 2007 PMID: 17905336

Text-mined citations for rs199472931...

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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 27, 2021