ClinVar Genomic variation as it relates to human health
NM_172201.2(KCNE2):c.22A>G (p.Thr8Ala)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance(1); Benign(6); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_172201.2(KCNE2):c.22A>G (p.Thr8Ala)
Variation ID: 67615 Accession: VCV000067615.34
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 21q22.11 21: 34370500 (GRCh38) [ NCBI UCSC ] 21: 35742799 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jul 5, 2015 Apr 15, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_172201.2:c.22A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_751951.1:p.Thr8Ala missense NC_000021.9:g.34370500A>G NC_000021.8:g.35742799A>G NG_008804.1:g.11477A>G LRG_291:g.11477A>G LRG_291t1:c.22A>G LRG_291p1:p.Thr8Ala Q9Y6J6:p.Thr8Ala - Protein change
- T8A
- Other names
- p.T8A:ACA>GCA
- Canonical SPDI
- NC_000021.9:34370499:A:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00140 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00387
1000 Genomes Project 0.00140
Trans-Omics for Precision Medicine (TOPMed) 0.00367
Exome Aggregation Consortium (ExAC) 0.00380
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00492
1000 Genomes Project 30x 0.00109
The Genome Aggregation Database (gnomAD), exomes 0.00372
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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KCNE2 | - | - |
GRCh38 GRCh37 |
1 | 217 | |
LOC105372791 | - | - | - | GRCh38 | - | 168 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Aug 21, 2023 | RCV000058368.27 | |
Benign (1) |
criteria provided, single submitter
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Jun 24, 2013 | RCV000171812.10 | |
Benign (1) |
criteria provided, single submitter
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Nov 8, 2011 | RCV000170566.12 | |
Benign (1) |
criteria provided, single submitter
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Jun 25, 2015 | RCV000248455.10 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Jan 8, 2024 | RCV000845300.13 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Jan 31, 2024 | RCV001086272.19 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Benign
(Jun 24, 2013)
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criteria provided, single submitter
Method: research
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Long QT syndrome, drug-associated
Affected status: unknown
Allele origin:
unknown
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Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000050773.2 First in ClinVar: Jun 04, 2015 Last updated: Sep 14, 2015 |
Number of individuals with the variant: 5
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Uncertain significance
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Long QT syndrome 6
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001299546.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
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)
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, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Benign
(Jun 25, 2015)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000318183.6
First in ClinVar: Oct 02, 2016 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Number of individuals with the variant: 1
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Long QT syndrome 6
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000252887.11
First in ClinVar: Oct 11, 2015 Last updated: Feb 14, 2024 |
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Benign
(Aug 21, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001159376.5
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
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Likely benign
(Jan 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004153596.4
First in ClinVar: Nov 20, 2023 Last updated: Apr 15, 2024 |
Comment:
KCNE2: BS2
Number of individuals with the variant: 3
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Benign
(Nov 08, 2011)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000169912.12
First in ClinVar: Jun 23, 2014 Last updated: Jul 05, 2015 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Likely benign
(-)
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criteria provided, single submitter
Method: clinical testing
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Long QT syndrome
Affected status: yes
Allele origin:
germline
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Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
Accession: SCV000987336.1
First in ClinVar: Sep 08, 2019 Last updated: Sep 08, 2019 |
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Benign
(Jan 08, 2024)
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criteria provided, single submitter
Method: research
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Long QT syndrome
Affected status: yes
Allele origin:
maternal
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Dept of Medical Biology, Uskudar University
Accession: SCV004022048.2
First in ClinVar: Jul 29, 2023 Last updated: Jan 26, 2024 |
Comment:
Criteria: PP3, BS1, BS2
Number of individuals with the variant: 1
Sex: female
Ethnicity/Population group: Turkish
Geographic origin: Turkey
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not provided
(-)
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no classification provided
Method: literature only
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not provided
Affected status: unknown
Allele origin:
germline
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Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust
Accession: SCV000089888.3
First in ClinVar: Oct 22, 2013 Last updated: Oct 09, 2016 |
Comment:
This variant has been reported in the following publications (PMID:10984545;PMID:11468227;PMID:12402336;PMID:14661677;PMID:14760488;PMID:15599693;PMID:17161064;PMID:17210839).
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Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. | Arnestad M | Circulation | 2007 | PMID: 17210839 |
Association of torsades de pointes with novel and known single nucleotide polymorphisms in long QT syndrome genes. | Mank-Seymour AR | American heart journal | 2006 | PMID: 17161064 |
Single nucleotide polymorphism map of five long-QT genes. | Aydin A | Journal of molecular medicine (Berlin, Germany) | 2005 | PMID: 15599693 |
Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. | Paulussen AD | Journal of molecular medicine (Berlin, Germany) | 2004 | PMID: 14760488 |
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 |
DHPLC analysis of potassium ion channel genes in congenital long QT syndrome. | Jongbloed R | Human mutation | 2002 | PMID: 12402336 |
Screening for mutations and polymorphisms in the genes KCNH2 and KCNE2 encoding the cardiac HERG/MiRP1 ion channel: implications for acquired and congenital long Q-T syndrome. | Larsen LA | Clinical chemistry | 2001 | PMID: 11468227 |
A common polymorphism associated with antibiotic-induced cardiac arrhythmia. | Sesti F | Proceedings of the National Academy of Sciences of the United States of America | 2000 | PMID: 10984545 |
MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. | Abbott GW | Cell | 1999 | PMID: 10219239 |
Text-mined citations for rs2234916 ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.