This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 231 of the KCNQ1 protein (p.Arg231His). This variant is present in population databases (rs199472709, gnomAD 0.3%). This missense change has been observed in individual(s) with long QT syndrome (PMID: 16414944, 23350853, 24861447). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 53087). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNQ1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects KCNQ1 function (PMID: 23350853). This variant disrupts the p.Arg231 amino acid residue in KCNQ1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15176425, 20850564, 22509038). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_000218.3(KCNQ1):c.692G>A (p.Arg231His)
Germline
Classification
Help
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.
(10)
Help
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.
Pathogenic
10
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.692G>A (p.Arg231His)
Variation ID: 53087 Accession: VCV000053087.18
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 11p15.5 11: 2572021 (GRCh38) [ NCBI UCSC ] 11: 2593251 (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 May 29, 2016 Sep 16, 2024 May 7, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000218.3:c.692G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000209.2:p.Arg231His missense NM_001406836.1:c.692G>A NP_001393765.1:p.Arg231His missense NM_001406837.1:c.422G>A NP_001393766.1:p.Arg141His missense NM_181798.2:c.311G>A NP_861463.1:p.Arg104His missense NR_040711.2:n.585G>A NC_000011.10:g.2572021G>A NC_000011.9:g.2593251G>A NG_008935.1:g.132031G>A LRG_287:g.132031G>A LRG_287t1:c.692G>A LRG_287p1:p.Arg231His LRG_287t2:c.311G>A LRG_287p2:p.Arg104His P51787:p.Arg231His - Protein change
- R231H, R104H, R141H
- Other names
-
p.R231H:CGC>CAC
- Canonical SPDI
- NC_000011.10:2572020:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD) 0.00003
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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 |
1726 | 2669 | |
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. |
|---|---|---|---|---|
| Pathogenic (1) |
criteria provided, single submitter
|
Nov 27, 2023 | RCV000046107.15 | |
| not provided (1) |
no classification provided
|
- | RCV000057734.4 | |
| Pathogenic (2) |
criteria provided, single submitter
|
May 22, 2022 | RCV000115007.5 | |
| Pathogenic (1) |
no assertion criteria provided
|
Sep 1, 2013 | RCV000115008.4 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
May 7, 2024 | RCV000182101.10 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Oct 31, 2018 | RCV000762833.3 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Mar 26, 2021 | RCV002371883.2 |
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Sep 05, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV003820885.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(Nov 27, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Long QT syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000074120.13
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 231 of the KCNQ1 protein (p.Arg231His). … (more)
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 231 of the KCNQ1 protein (p.Arg231His). This variant is present in population databases (rs199472709, gnomAD 0.3%). This missense change has been observed in individual(s) with long QT syndrome (PMID: 16414944, 23350853, 24861447). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 53087). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNQ1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects KCNQ1 function (PMID: 23350853). This variant disrupts the p.Arg231 amino acid residue in KCNQ1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15176425, 20850564, 22509038). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Oct 31, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Beckwith-Wiedemann syndrome
Long QT syndrome 1 Long QT syndrome 1 Jervell and Lange-Nielsen syndrome 1 Atrial fibrillation, familial, 3 Short QT syndrome type 2
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000893192.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
|
|
|
Pathogenic
(May 22, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Atrial fibrillation, familial, 3
Affected status: yes
Allele origin:
germline
|
3billion
Accession: SCV002521152.1
First in ClinVar: Jun 05, 2022 Last updated: Jun 05, 2022 |
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of … (more)
The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.96; 3Cnet: 1.00). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000053087). Different missense changes at the same codon (p.Arg231Cys, p.Arg231Leu, p.Arg231Ser) have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000053086, VCV000280173, VCV000519257). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Atrial fibrillation (present)
|
|
|
Pathogenic
(May 07, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000234404.14
First in ClinVar: Jul 05, 2015 Last updated: Sep 16, 2024 |
Comment:
Published functional studies demonstrate a gain of function evidenced by increased channel current and loss of voltage-dependent gating (PMID: 23350853); Not observed at a significant … (more)
Published functional studies demonstrate a gain of function evidenced by increased channel current and loss of voltage-dependent gating (PMID: 23350853); Not observed at a significant frequency in large population cohorts (gnomAD); Identified in several patients with LQTS and/or atrial fibrillation in published literature (PMID: 16414944, 18452873, 19716085, 23350853, 24861447, 31638414); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 19716085, 23851063, 24861447, 23350853, 18452873, 24721657, 24096004, 16414944, 34426522, Rida2023[article], Tamargo2017[article], 33600800, 31638414, 34750360) (less)
|
|
|
Pathogenic
(Mar 26, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002668225.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.R231H pathogenic mutation (also known as c.692G>A), located in coding exon 5 of the KCNQ1 gene, results from a G to A substitution at … (more)
The p.R231H pathogenic mutation (also known as c.692G>A), located in coding exon 5 of the KCNQ1 gene, results from a G to A substitution at nucleotide position 692. The arginine at codon 231 is replaced by histidine, an amino acid with highly similar properties, and is located within the S4 transmembrane voltage sensor of the potassium channel. This mutation has been reported in individuals with atrial fibrillation and/or prolonged QTc and demonstrated segregation with disease in affected family members in multiple families (Johnson JN et al. Heart Rhythm, 2008 May;5:704-9; Bartos DC et al. J Cardiovasc Electrophysiol, 2013 May;24:562-9; Napolitano C et al. JAMA, 2005 Dec;294:2975-80; Guerrier K et al. Heart Rhythm, 2013 Sep;10:1351-3; Goodyer WR et al. Circ Genom Precis Med, 2019 11;12:e002713). Functional studies demonstrated suppressed PKA regulation, increased KCNQ1 potassium current, and super-trafficking (Bartos DC et al. J Cardiovasc Electrophysiol, 2013 May;24:562-9; Huang H et al. J Biol Chem, 2021 Feb;:100423). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
|
|
|
Pathogenic
(Sep 01, 2013)
|
no assertion criteria provided
Method: literature only
|
ATRIAL FIBRILLATION, FAMILIAL, 3
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000148916.2
First in ClinVar: May 06, 2014 Last updated: Feb 06, 2017 |
Comment on evidence:
Johnson et al. (2008) reported a female patient with onset of atrial fibrillation (ATFB3; 607554) in the first year of life who was heterozygous for … (more)
Johnson et al. (2008) reported a female patient with onset of atrial fibrillation (ATFB3; 607554) in the first year of life who was heterozygous for a c.692G-A transition in exon 5 of the KCNQ1 gene, resulting in an arg231-to-his (R231H) substitution. The patient was also found to have a long QT interval (see 192500) at 1 year of age, with a QTc of 479 ms. In affected members of 4 families with early-onset atrial fibrillation, Bartos et al. (2013) identified heterozygosity for the R231H mutation in KCNQ1. Twelve of 13 mutation-positive individuals had a normal QTc, and 1 had a prolonged QT interval. Functional analysis indicated that the R231H mutation increases the amount of KCNQ1 current during the atrial action potential, thus dramatically shortening its duration. R231H also disrupts PKA (see 188830) regulation of the KCNQ1 current and is associated with borderline and adrenergic-induced QT interval prolongation in patients. In affected members of a family with atrial fibrillation, Guerrier et al. (2013) identified heterozygosity for the R231H missense mutation in KCNQ1. Guerrier et al. (2013) noted that the R231H mutation had previously been identified by Napolitano et al. (2005) in a study of patients with long QT syndrome, but stated that none of the family members with atrial fibrillation had documented prolonged QT intervals. (less)
|
|
|
Pathogenic
(Sep 01, 2013)
|
no assertion criteria provided
Method: literature only
|
LONG QT SYNDROME 1
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000148917.2
First in ClinVar: May 06, 2014 Last updated: Feb 06, 2017 |
Comment on evidence:
Johnson et al. (2008) reported a female patient with onset of atrial fibrillation (ATFB3; 607554) in the first year of life who was heterozygous for … (more)
Johnson et al. (2008) reported a female patient with onset of atrial fibrillation (ATFB3; 607554) in the first year of life who was heterozygous for a c.692G-A transition in exon 5 of the KCNQ1 gene, resulting in an arg231-to-his (R231H) substitution. The patient was also found to have a long QT interval (see 192500) at 1 year of age, with a QTc of 479 ms. In affected members of 4 families with early-onset atrial fibrillation, Bartos et al. (2013) identified heterozygosity for the R231H mutation in KCNQ1. Twelve of 13 mutation-positive individuals had a normal QTc, and 1 had a prolonged QT interval. Functional analysis indicated that the R231H mutation increases the amount of KCNQ1 current during the atrial action potential, thus dramatically shortening its duration. R231H also disrupts PKA (see 188830) regulation of the KCNQ1 current and is associated with borderline and adrenergic-induced QT interval prolongation in patients. In affected members of a family with atrial fibrillation, Guerrier et al. (2013) identified heterozygosity for the R231H missense mutation in KCNQ1. Guerrier et al. (2013) noted that the R231H mutation had previously been identified by Napolitano et al. (2005) in a study of patients with long QT syndrome, but stated that none of the family members with atrial fibrillation had documented prolonged QT intervals. (less)
|
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Pathogenic
(Apr 06, 2017)
|
no assertion criteria provided
Method: provider interpretation
|
not provided
Affected status: unknown
Allele origin:
germline
|
Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000924827.1
First in ClinVar: Jun 29, 2019 Last updated: Jun 29, 2019 |
|
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
Congenital long QT syndrome
Affected status: unknown
Allele origin:
germline
|
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust
Accession: SCV000089253.3
First in ClinVar: Oct 22, 2013 Last updated: Oct 09, 2016 |
Comment:
This variant has been reported as associated with Long QT syndrome in the following publications (PMID:16414944;PMID:19716085). This is a literature report, and does not necessarily … (more)
This variant has been reported as associated with Long QT syndrome in the following publications (PMID:16414944;PMID:19716085). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. (less)
|
Comment:
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.96; 3Cnet: 1.00). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000053087). Different missense changes at the same codon (p.Arg231Cys, p.Arg231Leu, p.Arg231Ser) have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000053086, VCV000280173, VCV000519257). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Comment:
Published functional studies demonstrate a gain of function evidenced by increased channel current and loss of voltage-dependent gating (PMID: 23350853); Not observed at a significant frequency in large population cohorts (gnomAD); Identified in several patients with LQTS and/or atrial fibrillation in published literature (PMID: 16414944, 18452873, 19716085, 23350853, 24861447, 31638414); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 19716085, 23851063, 24861447, 23350853, 18452873, 24721657, 24096004, 16414944, 34426522, Rida2023[article], Tamargo2017[article], 33600800, 31638414, 34750360)
Comment:
The p.R231H pathogenic mutation (also known as c.692G>A), located in coding exon 5 of the KCNQ1 gene, results from a G to A substitution at nucleotide position 692. The arginine at codon 231 is replaced by histidine, an amino acid with highly similar properties, and is located within the S4 transmembrane voltage sensor of the potassium channel. This mutation has been reported in individuals with atrial fibrillation and/or prolonged QTc and demonstrated segregation with disease in affected family members in multiple families (Johnson JN et al. Heart Rhythm, 2008 May;5:704-9; Bartos DC et al. J Cardiovasc Electrophysiol, 2013 May;24:562-9; Napolitano C et al. JAMA, 2005 Dec;294:2975-80; Guerrier K et al. Heart Rhythm, 2013 Sep;10:1351-3; Goodyer WR et al. Circ Genom Precis Med, 2019 11;12:e002713). Functional studies demonstrated suppressed PKA regulation, increased KCNQ1 potassium current, and super-trafficking (Bartos DC et al. J Cardiovasc Electrophysiol, 2013 May;24:562-9; Huang H et al. J Biol Chem, 2021 Feb;:100423). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Comment:
This variant has been reported as associated with Long QT syndrome in the following publications (PMID:16414944;PMID:19716085). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
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:
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 231 of the KCNQ1 protein (p.Arg231His). This variant is present in population databases (rs199472709, gnomAD 0.3%). This missense change has been observed in individual(s) with long QT syndrome (PMID: 16414944, 23350853, 24861447). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 53087). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNQ1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects KCNQ1 function (PMID: 23350853). This variant disrupts the p.Arg231 amino acid residue in KCNQ1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15176425, 20850564, 22509038). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.96; 3Cnet: 1.00). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000053087). Different missense changes at the same codon (p.Arg231Cys, p.Arg231Leu, p.Arg231Ser) have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000053086, VCV000280173, VCV000519257). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Comment:
Published functional studies demonstrate a gain of function evidenced by increased channel current and loss of voltage-dependent gating (PMID: 23350853); Not observed at a significant frequency in large population cohorts (gnomAD); Identified in several patients with LQTS and/or atrial fibrillation in published literature (PMID: 16414944, 18452873, 19716085, 23350853, 24861447, 31638414); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 19716085, 23851063, 24861447, 23350853, 18452873, 24721657, 24096004, 16414944, 34426522, Rida2023[article], Tamargo2017[article], 33600800, 31638414, 34750360)
Comment:
The p.R231H pathogenic mutation (also known as c.692G>A), located in coding exon 5 of the KCNQ1 gene, results from a G to A substitution at nucleotide position 692. The arginine at codon 231 is replaced by histidine, an amino acid with highly similar properties, and is located within the S4 transmembrane voltage sensor of the potassium channel. This mutation has been reported in individuals with atrial fibrillation and/or prolonged QTc and demonstrated segregation with disease in affected family members in multiple families (Johnson JN et al. Heart Rhythm, 2008 May;5:704-9; Bartos DC et al. J Cardiovasc Electrophysiol, 2013 May;24:562-9; Napolitano C et al. JAMA, 2005 Dec;294:2975-80; Guerrier K et al. Heart Rhythm, 2013 Sep;10:1351-3; Goodyer WR et al. Circ Genom Precis Med, 2019 11;12:e002713). Functional studies demonstrated suppressed PKA regulation, increased KCNQ1 potassium current, and super-trafficking (Bartos DC et al. J Cardiovasc Electrophysiol, 2013 May;24:562-9; Huang H et al. J Biol Chem, 2021 Feb;:100423). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Comment:
This variant has been reported as associated with Long QT syndrome in the following publications (PMID:16414944;PMID:19716085). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Disease-linked supertrafficking of a potassium channel. | Huang H | The Journal of biological chemistry | 2021 | PMID: 33600800 |
| Broad Genetic Testing in a Clinical Setting Uncovers a High Prevalence of Titin Loss-of-Function Variants in Very Early Onset Atrial Fibrillation. | Goodyer WR | Circulation. Genomic and precision medicine | 2019 | PMID: 31638414 |
| Impaired Adrenergic/Protein Kinase A Response of Slow Delayed Rectifier Potassium Channels as a Long QT Syndrome Motif: Importance and Unknowns. | Policarová M | The Canadian journal of cardiology | 2019 | PMID: 30935642 |
| Early repolarization is associated with symptoms in patients with type 1 and type 2 long QT syndrome. | Laksman ZW | Heart rhythm | 2014 | PMID: 24861447 |
| Long QT genetics manifesting as atrial fibrillation. | Guerrier K | Heart rhythm | 2013 | PMID: 23851063 |
| A KCNQ1 mutation causes a high penetrance for familial atrial fibrillation. | Bartos DC | Journal of cardiovascular electrophysiology | 2013 | PMID: 23350853 |
| Allosteric gating mechanism underlies the flexible gating of KCNQ1 potassium channels. | Osteen JD | Proceedings of the National Academy of Sciences of the United States of America | 2012 | PMID: 22509038 |
| R231C mutation in KCNQ1 causes long QT syndrome type 1 and familial atrial fibrillation. | Bartos DC | Heart rhythm | 2011 | PMID: 20850564 |
| 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 |
| Prevalence of early-onset atrial fibrillation in congenital long QT syndrome. | Johnson JN | Heart rhythm | 2008 | PMID: 18452873 |
| Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. | Napolitano C | JAMA | 2005 | PMID: 16414944 |
| Four potassium channel mutations account for 73% of the genetic spectrum underlying long-QT syndrome (LQTS) and provide evidence for a strong founder effect in Finland. | Fodstad H | Annals of medicine | 2004 | PMID: 15176425 |
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Text-mined citations for rs199472709 ...
HelpThese 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 Sep 29, 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.