ClinVar Genomic variation as it relates to human health
NM_000218.3(KCNQ1):c.569G>A (p.Arg190Gln)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000218.3(KCNQ1):c.569G>A (p.Arg190Gln)
Variation ID: 3117 Accession: VCV000003117.29
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p15.5 11: 2570719 (GRCh38) [ NCBI UCSC ] 11: 2591949 (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 Apr 4, 2013 Apr 20, 2024 Jan 17, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000218.3:c.569G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000209.2:p.Arg190Gln missense NM_001406836.1:c.569G>A NP_001393765.1:p.Arg190Gln missense NM_001406837.1:c.299G>A NP_001393766.1:p.Arg100Gln missense NM_181798.2:c.188G>A NP_861463.1:p.Arg63Gln missense NR_040711.2:n.462G>A NC_000011.10:g.2570719G>A NC_000011.9:g.2591949G>A NG_008935.1:g.130729G>A LRG_287:g.130729G>A LRG_287t1:c.569G>A LRG_287p1:p.Arg190Gln LRG_287t2:c.188G>A LRG_287p2:p.Arg63Gln P51787:p.Arg190Gln - Protein change
- R190Q, R63Q, R100Q
- Other names
- p.R190Q:CGG>CAG
- Canonical SPDI
- NC_000011.10:2570718:G:A
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD) 0.00002
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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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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KCNQ1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh38 GRCh37 |
1696 | 2580 |
Conditions - Germline
Condition
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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
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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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Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Nov 24, 2021 | RCV000003264.16 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 17, 2024 | RCV000046088.21 | |
Likely pathogenic (2) |
criteria provided, single submitter
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Jun 30, 2022 | RCV000057706.12 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Nov 29, 2021 | RCV000182086.20 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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May 21, 2018 | RCV000588393.11 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 26, 2019 | RCV001841223.10 |
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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Pathogenic
(Jan 01, 2013)
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criteria provided, single submitter
Method: research
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Long QT syndrome, LQT1 subtype
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital
Study: Life Threatening Long QT Syndromes
Accession: SCV000240225.2 First in ClinVar: Jul 01, 2016 Last updated: Jul 01, 2016 |
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: Indian
Geographic origin: India
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Pathogenic
(May 05, 2017)
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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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695991.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The KCNQ1 c.569G>A (p.Arg190Gln) variant causes a missense change involving the alteration of a highly conserved nucleotide. The variant is located within S2S3 … (more)
Variant summary: The KCNQ1 c.569G>A (p.Arg190Gln) variant causes a missense change involving the alteration of a highly conserved nucleotide. The variant is located within S2S3 cytoplasmic loop of transmembrane domain and 4/5 in silico tools predict a damaging outcome for this variant. The Arg190Gln was to proven to be a functionally abrogated by experimental studies where mutation led to a non-functional channel, independently of the presence of stimulation subunit IsK (Chouabe, 2000; Wang, 1999). The c.1550G>A was not identified in large, broad control datasets of ExAC and gnomAD (~120332 and ~246272 chrs tested, respectively), but is found in multiple LQTS individuals and segregated with the disease in several families (Wang, 1996; Chouabe, 2000; Gao, 2012). In addition, Arg190 appears to be a mutational hot-spot, as other alterations of this codon have been reported in association with LQTS (p.Arg190Leu, p.Arg190Trp). Lastly, multiple clinical diagnostic laboratories/reputable databases classified this variant as Pathogenic. Taken together, this variant is classified as Pathogenic. (less)
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal unknown)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447883.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Prolonged QTc interval (present)
Sex: female
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Pathogenic
(Mar 19, 2020)
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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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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001713550.1
First in ClinVar: Jun 15, 2021 Last updated: Jun 15, 2021 |
Comment:
PP1_Strong, PS3_Moderate; PS4_Moderate, PM2, PM3, PM5, PM1, PP3
Number of individuals with the variant: 1
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Pathogenic
(Nov 26, 2019)
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criteria provided, single submitter
Method: clinical testing
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Cardiac arrhythmia
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV001346705.2
First in ClinVar: Jun 22, 2020 Last updated: Jan 14, 2022 |
Comment:
This missense variant replaces arginine with glutamine at codon 190 of the KCNQ1 protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
This missense variant replaces arginine with glutamine at codon 190 of the KCNQ1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant causes a loss of KCNQ1 channel activity (PMID: 10376919, 10728423, 20660394). This variant has been reported in individuals affected with long QT syndrome (PMID: 17470695, 19841300, 21350584, 22949429, 23075154, 8528244, 10728423, 20660394) and in individuals affected with Jervell and Lange-Nielsen syndrome (PMID: 22629021, 27485560). This variant has been shown to segregate with disease in multiple families affected with long QT syndrome (PMID: 8528244, 10728423, 20660394). This variant has been identified in 1/249462 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(May 21, 2018)
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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: SCV000737871.4
First in ClinVar: Apr 13, 2018 Last updated: Mar 04, 2023 |
Comment:
The p.R190Q pathogenic mutation (also known as c.569G>A), located in coding exon 3 of the KCNQ1 gene, results from a G to A substitution at … (more)
The p.R190Q pathogenic mutation (also known as c.569G>A), located in coding exon 3 of the KCNQ1 gene, results from a G to A substitution at nucleotide position 569. The arginine at codon 190 is replaced by glutamine, an amino acid with highly similar properties, and is located in the S2/S3 transmembrane spanning region of the protein. This mutation has been reported numerous times in individuals with long QT syndrome (LQTS) and in LQTS cohorts, and it has segregated with disease in several families (Wang Q et al. Nat. Genet. 1996;12:17-23; Chouabe C et al. Cardiovasc. Res. 2000;45:971-80; Moss AJ et al. Circulation. 2007;115:2481-9; Kapplinger JD et al. Heart Rhythm. 2009;6:1297-303; Moretti A et al. N. Engl. J. Med. 2010;363:1397-409). The p.R190Q mutation has also been detected in the homozygous and compound heterozygous states in Jervell and Lange-Nielsen syndrome (JLNS) patients (Gao Y et al. J Cardiovasc Dis Res. 2012;3:67-75; Vyas B et al. Am. J. Med. Genet. A. 2016;170:1510-9). Functional studies have demonstrated that p.R190Q disrupts KCNQ1 protein function, likely as a result of a trafficking defect, causing a reduction in the potassium current (Chouabe C et al. Cardiovasc. Res. 2000;45:971-80; Moretti A et al. N. Engl. J. Med. 2010;363:1397-409; Barsheshet A et al. Circulation. 2012;125:1988-96; Chen Z et al. Eur. Heart J. 2016;epub:ehw189). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Likely Pathogenic
(Jun 30, 2022)
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criteria provided, single submitter
Method: clinical testing
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Congenital long QT syndrome
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004848631.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The p.Arg190Gln variant in KCNQ1 has been reported in at least 10 individuals with Long QT syndrome (LQTS) and segregated with disease in 6 affected … (more)
The p.Arg190Gln variant in KCNQ1 has been reported in at least 10 individuals with Long QT syndrome (LQTS) and segregated with disease in 6 affected individuals from 2 families (Wang 1996 PMID: 8528244, Wang 1999 PMID: 10376919, Chouabe 2000 PMID: 10728423, Barsheshet 2012 PMID: 22456477, Gao 2012 PMID: 22629021, Giudicessi 2012 PMID: 22949429, Ebrahim 2017 PMID: 28532774, Marschall 2019 PMID: 31737537, Westphal 2020 PMID: 32383558, Choi 2021 PMID: 34319147). It has also been identified in 1/113014 of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant has also been reported in ClinVar (Variation ID 3117). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In vitro and in vivo functional studies support an impact on protein function (Wang 1999 PMID: 10376919, Chouabe 2000 PMID: 10728423, Barsheshet 2012 PMID: 22456477). Another variant involving this codon (p.Arg190Leu) has been identified in individuals with LQTS and is classified as likely pathogenic by this laboratory. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant LQTS. ACMG/AMP Criteria applied: PS4_Moderate, PM5, PP1_Moderate, PM2_Supporting, PP3, PS3_Moderate. (less)
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Pathogenic
(May 26, 2020)
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criteria provided, single submitter
Method: clinical testing
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Long QT syndrome 1
Affected status: yes
Allele origin:
germline
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Clinical Genetics Laboratory, Region Ostergotland
Accession: SCV001984983.1
First in ClinVar: Oct 30, 2021 Last updated: Oct 30, 2021 |
Comment:
PS3, PS4, PM1, PM2, PP1, PP3, PP5, BP2, BP5
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Pathogenic
(Nov 24, 2021)
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criteria provided, single submitter
Method: clinical testing
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Long QT syndrome 1
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002581267.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
Number of individuals with the variant: 1
Sex: female
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Pathogenic
(Nov 29, 2021)
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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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GeneDx
Accession: SCV000234389.15
First in ClinVar: Jul 05, 2015 Last updated: Mar 04, 2023 |
Comment:
Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Functional studies in both mammalian cultured cells and induced pluripotent stem … (more)
Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Functional studies in both mammalian cultured cells and induced pluripotent stem cell-derived cardiomyocytes showed that the co-expression wild-type and R190Q mutant channels alters the delayed rectifier potassium current through a dominant negative effect (Chouabe et al., 2000; Moretti et al., 2010); 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: 23158531, 25825456, 27916777, 27041150, 22456477, 22629021, 10376919, 19862833, 10973849, 19716085, 17470695, 21350584, 15840476, 19841300, 14678125, 20660394, 27470144, 28182229, 22949429, 27485560, 28532774, 9386136, 8528244, 10728423, 28573431, 27917693, 30428582, 31737537, 32383558, 32665702) (less)
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Pathogenic
(Jan 17, 2024)
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criteria provided, single submitter
Method: clinical testing
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Long QT syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000074101.13
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 190 of the KCNQ1 protein (p.Arg190Gln). … (more)
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 190 of the KCNQ1 protein (p.Arg190Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with Jervell and Lange-Nielsen syndrome and/or long QT syndrome (PMID: 8528244, 10728423, 17470695, 20660394, 22629021). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as p.Arg61Gln. ClinVar contains an entry for this variant (Variation ID: 3117). 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: 10376919, 10728423). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Oct 07, 2010)
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no assertion criteria provided
Method: literature only
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LONG QT SYNDROME 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000023422.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In a family with 2 members affected by LQT1 (192500), Wang et al. (1996) used SSCP analysis to demonstrate a CGG (arg) to CAG (gln) … (more)
In a family with 2 members affected by LQT1 (192500), Wang et al. (1996) used SSCP analysis to demonstrate a CGG (arg) to CAG (gln) transition in codon 95 of the KVLQT1 gene. (This variant used to be known as ARG61GLN and ARG95GLN.) Moretti et al. (2010) reported the creation of patient-specific induced pluripotent stem (IPS) cells containing the R190Q mutation in KCNQ1. They compared IPS cells derived from dermal fibroblasts from 2 patients with this mutation with those from 2 control individuals. The cells were able to generate functional myocytes that showed a ventricular, atrial, or nodal phenotype, as evidenced by expression of cell type-specific markers and as seen in recordings of the action potentials in single cells. The duration of the action potential was markedly prolonged in ventricular and atrial cells derived from patients with LQTS1, as compared with cells from control subjects. Further characterization of the role of the R190Q KCNQ1 mutation in the pathogenesis of LQTS1 revealed a dominant-negative trafficking defect associated with a 70 to 80% reduction in I(Ks) current and altered channel activation and deactivation properties. Moreover, Moretti et al. (2010) showed that myocytes derived from patients with LQTS1 had an increased susceptibility to catecholamine-induced tachyarrhythmia and that beta-blockade attenuated this phenotype, as was demonstrated in the patients themselves. (less)
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Pathogenic
(Dec 02, 2014)
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no assertion criteria provided
Method: clinical testing
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Not provided
Affected status: not provided
Allele origin:
germline
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Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000280158.1
First in ClinVar: May 29, 2016 Last updated: May 29, 2016 |
Comment:
Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case … (more)
Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. KCNQ1 p.Arg190Gln Given the strong case data and absence in controls, we consider this variant to be very likely disease causing. This variant has been seen in at least 10 unrelated cases of Long QT syndrome with moderate segregation data. This variant was previously reported as p.Arg61Gln and p.Arg95Gln. Wang et al (1996) identified KCNQ1 as the LQT1 locus and reported the first KCNQ1 variants, including p.Arg190Gln in a family with two affected individuals (reported as p.Arg61Gln). Donger et al (1997) observed the the variant in a family with long QT from their French cohort. It appears that multiple affected family members had the variant, though it is unclear from the data presented how many. Chouabe et al (2000) reported a family with long QT syndrome and the p.Arg190Gln variant. Of the four individuals in the family who carried the variant, three had a prolonged QT interval (472-530ms). Larsen et al (2001) observed the variant in a long QT patient from their Dutch cohort. Westenskow et al (2004) (Keating's group) observed the variant in a family with long QT syndrome who also carried a variant in KCNE1. The variant is reported in the Familion compendium in 3 of 2500 patients referred for clinical long QT genetic testing (Kapplinger et al 2009, likely same cases as Kapa et al 2009). Of note in considering the other cases reported by Kapplinger et al (2009) is the lack of phenotypic data on this cohort, the low yield of 36% (vs. 70% in cohorts with firm diagnoses of long QT), and the lack of clarity regarding which variants were seen with another variant (9% of the cohort had multiple variants). Gao et al reported the variant in a patient from their Chinese cohort with JLNS who was a compound heterozygote. Hofman et al (2010) reported on 14 long QT syndrome variants, including this one, that were found recurrently in the Netherlands. The p.Arg190Gln variant was seen in three different probands. The variant was included in several papers on genotype-phenotype correlations, however the cases likely overlap with prior reports (Moss et al 2007, Barsheshet et al 2012). We have seen this variant in one other family in our center, present in both mother and son with long QT syndrome. (note that the cases reported by Wang et al, Zareba et al, Moss et al, and Horr et al may not be unique) Chouabe et al (2000) reported that the variant led to a non-functional channel in their studies. Moretti et al (2010) studied patient-specific IPS cells with the p.Arg190Gln variant and observed a dominant-negative trafficking defect associated with a reduction in the I(Ks) current and altered channel activation and deactivation properties. The variant occurs in the S2-S3 domain, one of the cytoplasmic loops. Variants in this region are likely to pathogenic (Kapa et al 2009). Moss et al (2007) classified the variant's effect as haploinsufficient and found that such variants confer a lower risk of arrhythmias than variants with a dominant negative effect. However, a later report from the same group re-classified the effect as dominant negative (Barsheshet et al 2012). This same study also found a higher risk of events, as well as a greater response to beta-blockers, associated with variants in the cytoplasmic loop. In silico analysis with PolyPhen-2 predicts the variant to be probably damaging; SIFT predicts it to be deleterious. Other variants have been reported in association with disease at this codon (p.Arg190Leu, p.Arg190Trp) and nearby codons (p.Lys183Arg, p.Lys183Met, p.Tyr184His, p.Tyr184Ser, p.Gly186Arg, p.Gly186Ser, p.Leu187Pro, p.Gly189Glu, p.Gly189Arg, p.Leu191Pro, p.Arg192His, p.Arg192Pro, p.Arg192Cys, p.Phe193Leu, p.Ala94Pro, p.Arg195Gln, p.Arg195Trp, p.Ile98Val, p.Ser199Ala). In total the variant has not been seen in ~8000 published controls and individuals from publicly available population datasets. There is no variation at codon 190 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on 6500 Caucasian and African American individuals (as of December 27th, 2013). The variant was not observed in the following lpublished control samples: Wang et al (1996) did not observe the variant in over 200 control individuals, Kapplinger et al (2009) did not observe the variant in 1300 presumed healthy individuals. The variant is listed in dbSNP (rs120074178) as a pathogenic variant. (less)
Number of individuals with the variant: 10
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not provided
(-)
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no classification provided
Method: literature only
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Congenital long QT syndrome
Affected status: unknown
Allele origin:
germline
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Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust
Accession: SCV000089225.3
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:8528244;PMID:9386136;PMID:10728423;PMID:11668638;PMID:14678125;PMID:15051636;PMID:15840476;PMID:19716085;PMID:19841300;PMID:10376919;PMID:17470695;PMID:9693036;PMID:22456477;PMID:22629021). 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:8528244;PMID:9386136;PMID:10728423;PMID:11668638;PMID:14678125;PMID:15051636;PMID:15840476;PMID:19716085;PMID:19841300;PMID:10376919;PMID:17470695;PMID:9693036;PMID:22456477;PMID:22629021). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. (less)
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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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Genotype Positive Long QT Syndrome in Patients With Coexisting Congenital Heart Disease. | Ebrahim MA | The American journal of cardiology | 2017 | PMID: 28532774 |
Phenotype guided characterization and molecular analysis of Indian patients with long QT syndromes. | Vyas B | Indian pacing and electrophysiology journal | 2016 | PMID: 27485560 |
KCNQ1 mutations associated with Jervell and Lange-Nielsen syndrome and autosomal recessive Romano-Ward syndrome in India-expanding the spectrum of long QT syndrome type 1. | Vyas B | American journal of medical genetics. Part A | 2016 | PMID: 27041150 |
Efficacy of ventricular pacing in the treatment of an arrhythmic storm associated with a congenital long QT mutation. | Aziz PF | Congenital heart disease | 2013 | PMID: 23075154 |
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 |
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 |
Genotype-phenotype analysis of three Chinese families with Jervell and Lange-Nielsen syndrome. | Gao Y | Journal of cardiovascular disease research | 2012 | PMID: 22629021 |
Mutations in cytoplasmic loops of the KCNQ1 channel and the risk of life-threatening events: implications for mutation-specific response to β-blocker therapy in type 1 long-QT syndrome. | Barsheshet A | Circulation | 2012 | PMID: 22456477 |
Recurrent and Founder Mutations in the Netherlands: the Long-QT Syndrome. | Hofman N | Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation | 2011 | PMID: 21350584 |
Patient-specific induced pluripotent stem-cell models for long-QT syndrome. | Moretti A | The New England journal of medicine | 2010 | PMID: 20660394 |
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 |
Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene. | Moss AJ | Circulation | 2007 | PMID: 17470695 |
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 |
Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. | Tester DJ | Heart rhythm | 2005 | PMID: 15840476 |
Compound mutations: a common cause of severe long-QT syndrome. | Westenskow P | Circulation | 2004 | PMID: 15051636 |
Location of mutation in the KCNQ1 and phenotypic presentation of long QT syndrome. | Zareba W | Journal of cardiovascular electrophysiology | 2003 | PMID: 14678125 |
KCNQ1 gain-of-function mutation in familial atrial fibrillation. | Chen YH | Science (New York, N.Y.) | 2003 | PMID: 12522251 |
Automated mutation screening using dideoxy fingerprinting and capillary array electrophoresis. | Larsen LA | Human mutation | 2001 | PMID: 11668638 |
Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. | Splawski I | Circulation | 2000 | PMID: 10973849 |
Novel mutations in KvLQT1 that affect Iks activation through interactions with Isk. | Chouabe C | Cardiovascular research | 2000 | PMID: 10728423 |
Functional effects of mutations in KvLQT1 that cause long QT syndrome. | Wang Z | Journal of cardiovascular electrophysiology | 1999 | PMID: 10376919 |
Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1. | Splawski I | Genomics | 1998 | PMID: 9693036 |
KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome. | Donger C | Circulation | 1997 | PMID: 9386136 |
Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. | Wang Q | Nature genetics | 1996 | PMID: 8528244 |
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Text-mined citations for rs120074178 ...
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.