VCV000036436.32 - ClinVar

NM_000218.3(KCNQ1):c.1590+14T>C

Germline

Classification

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.

(17)

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.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000218.3(KCNQ1):c.1590+14T>C

Variation ID: 36436 Accession: VCV000036436.32

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p15.5 11: 2768933 (GRCh38) [ NCBI UCSC ] 11: 2790163 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Apr 4, 2013	Sep 29, 2024	Feb 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000218.3:c.1590+14T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_001406836.1:c.1494+14T>C		intron variant
NM_001406837.1:c.1320+14T>C		intron variant
NM_001406838.1:c.1050+14T>C		intron variant
NM_181798.2:c.1209+14T>C		intron variant
NC_000011.10:g.2768933T>C
NC_000011.9:g.2790163T>C
NG_008935.1:g.328943T>C
LRG_287:g.328943T>C
LRG_287t1:c.1590+14T>C

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000011.10:2768932:T:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

0.04613 (C)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.08607

Exome Aggregation Consortium (ExAC) 0.08683

Trans-Omics for Precision Medicine (TOPMed) 0.07302

The Genome Aggregation Database (gnomAD) 0.07860

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.08599

1000 Genomes Project 30x 0.04466

1000 Genomes Project 0.04613

Links

ClinGen: CA005973 dbSNP: rs11024034 VarSome

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
Gene	OMIM	HI score Help 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.
KCNQ1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38 GRCh37	1720	2663

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.
not specified	Benign (6)	criteria provided, multiple submitters, no conflicts	Jun 14, 2012	RCV000035342.23
Short QT syndrome type 2	Benign (1)	criteria provided, single submitter	Jan 13, 2018	RCV000283709.13
Long QT syndrome 1	Benign (1)	criteria provided, single submitter	Jan 13, 2018	RCV000298782.13
Congenital long QT syndrome	Likely benign (1)	criteria provided, single submitter	Jun 14, 2016	RCV000343301.13
Atrial fibrillation, familial, 3	Benign (1)	criteria provided, single submitter	Jan 13, 2018	RCV000335028.13
Jervell and Lange-Nielsen syndrome 1	Benign (1)	criteria provided, single submitter	Jan 13, 2018	RCV000405757.13
not provided	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Nov 29, 2023	RCV001355532.18
Cardiac arrhythmia	Benign (1)	criteria provided, single submitter	Aug 18, 2011	RCV001841534.10
Long QT syndrome	Benign (2)	criteria provided, single submitter	Feb 1, 2024	RCV002054499.16

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.
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000303044.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Jun 14, 2012)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000169944.11 First in ClinVar: Jun 23, 2014 Last updated: Oct 02, 2016	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)
Benign (May 07, 2012)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000058990.5 First in ClinVar: May 03, 2013 Last updated: Oct 02, 2016	Comment: 1590+14T>C in Intron 12 of KCNQ1: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus … (more) 1590+14T>C in Intron 12 of KCNQ1: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 11.5% (806/7020) of European American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS; dbSNP rs11024034). (less) Number of individuals with the variant: 287
Likely benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Romano-Ward Syndrome Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000370357.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Short QT syndrome type 2 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000370356.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Atrial fibrillation, familial, 3 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000370360.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Jervell and Lange-Nielsen syndrome 1 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000370358.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Long QT syndrome 1 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000370359.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
benign (Aug 18, 2011)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Arrhythmia (autosomal unknown) Affected status: not provided Allele origin: not applicable	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000052763.2 First in ClinVar: Apr 04, 2013 Last updated: Apr 12, 2022	Publications: PubMed (2) PubMed: 14760488‚ 16132053 Comment: Converted during submission to Benign.
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Long QT syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002401743.3 First in ClinVar: Apr 12, 2022 Last updated: Feb 20, 2024
Benign (Nov 29, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV002048898.4 First in ClinVar: Jan 08, 2022 Last updated: Feb 20, 2024
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005223185.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Uncertain significance (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: unknown	Department of Pathology and Laboratory Medicine, Sinai Health System Additional submitter: Franklin by Genoox Study: The Canadian Open Genetics Repository (COGR) Accession: SCV001550450.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021	Comment: multiple AR variants in same gene - keep for nowAllele frequency is common in at least one population database (frequency: 12.169% in gnomAD_ExomesFounderPop) based on … (more) multiple AR variants in same gene - keep for nowAllele frequency is common in at least one population database (frequency: 12.169% in gnomAD_ExomesFounderPop) based on the frequency threshold of 0.868% for this gene.Variant was observed in a homozygous state in population databases more than expected for disease.A synonymous variant not located in a splice region. (less)
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes 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: SCV001925741.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Likely benign (Sep 23, 2022)	no assertion criteria provided (ACMG Guidelines, 2015) Method: clinical testing	Long QT syndrome Affected status: yes Allele origin: germline	Cohesion Phenomics Accession: SCV003803666.1 First in ClinVar: Feb 18, 2023 Last updated: Feb 18, 2023
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001960118.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001972496.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
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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 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.

Comment:

1590+14T>C in Intron 12 of KCNQ1: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 11.5% (806/7020) of European American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS; dbSNP rs11024034).

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Comment:

multiple AR variants in same gene - keep for nowAllele frequency is common in at least one population database (frequency: 12.169% in gnomAD_ExomesFounderPop) based on the frequency threshold of 0.868% for this gene.Variant was observed in a homozygous state in population databases more than expected for disease.A synonymous variant not located in a splice region.

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Association of KCNQ1, KCNE1, KCNH2 and SCN5A polymorphisms with QTc interval length in a healthy population.	Gouas L	European journal of human genetics : EJHG	2005	PMID: 16132053
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

Text-mined citations for rs11024034 ...

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 27, 2024

ClinVar Genomic variation as it relates to human health

NM_000218.3(KCNQ1):c.1590+14T>C

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs11024034 ...