Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_181798.1(KCNQ1):c.584C>T (p.Thr195Met)

Help
Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
5 (Most recent: Sep 25, 2021)
Last evaluated:
Nov 4, 2020
Accession:
VCV000053151.7
Variation ID:
53151
Description:
single nucleotide variant
Help

NM_181798.1(KCNQ1):c.584C>T (p.Thr195Met)

Allele ID
67819
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
11p15.5
Genomic location
11: 2583478 (GRCh38) GRCh38 UCSC
11: 2604708 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P51787:p.Thr322Met
LRG_287t2:c.584C>T LRG_287p2:p.Thr195Met
LRG_287:g.143488C>T
... more HGVS
Protein change
T322M, T195M
Other names
p.T322M:ACG>ATG
Canonical SPDI
NC_000011.10:2583477:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00000
Links
ClinGen: CA008957
UniProtKB: P51787#VAR_074692
dbSNP: rs199472755
Varsome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, single submitter Aug 9, 2020 RCV000190213.6
Pathogenic 1 criteria provided, single submitter Nov 4, 2020 RCV000182149.3
Pathogenic 1 criteria provided, single submitter Aug 16, 2018 RCV000247480.1
not provided 1 no assertion provided - RCV000057831.3
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
KCNQ1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh38
GRCh37
1161 1427

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Nov 04, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000234452.11
Submitted: (Sep 25, 2021)
Evidence details
Comment:
Identified in multiple unrelated patients with LQTS either referred for genetic testing at GeneDx or in published literature (Napolitano et al., 2005; Zhang et al., … (more)
Pathogenic
(Aug 16, 2018)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000320507.5
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (11)
Comment:
The p.T322M pathogenic mutation (also known as c.965C>T), located in coding exon 7 of the KCNQ1 gene, results from a C to T substitution at … (more)
Pathogenic
(Aug 09, 2020)
criteria provided, single submitter
Method: clinical testing
Long QT syndrome
Allele origin: germline
Invitae
Accession: SCV000074196.8
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change replaces threonine with methionine at codon 322 of the KCNQ1 protein (p.Thr322Met). The threonine residue is highly conserved and there is a … (more)
Likely pathogenic
(-)
no assertion criteria provided
Method: research
Long QT syndrome
Allele origin: germline
Medical Research Institute,Tokyo Medical and Dental University
Additional submitter:
Division of Diabetes and Metabolic Diseases,Graduate School of Medicine, University of Tokyo
Accession: SCV000222064.1
Submitted: (Apr 16, 2015)
Evidence details
Publications
PubMed (1)
not provided
(-)
no assertion provided
Method: literature only
Congenital long QT syndrome
Allele origin: germline
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust
Accession: SCV000089351.3
Submitted: (Sep 22, 2016)
Evidence details
Publications
PubMed (5)
Comment:
This variant has been reported as associated with Long QT syndrome in the following publications (PMID:16414944;PMID:18400097;PMID:19716085;PMID:17470695). This is a literature report, and does not necessarily … (more)

Functional evidence

Help
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

Help
Title Author Journal Year Link
Left Ventricular Isovolumetric Relaxation Time Is Prolonged in Fetal Long-QT Syndrome. Clur SB Circulation. Arrhythmia and electrophysiology 2018 PMID: 29654130
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Identification of KCNQ1 compound heterozygous mutations in three Chinese families with Jervell and Lange-Nielsen Syndrome. Wang C Acta oto-laryngologica 2017 PMID: 27917693
Structural interplay of K<sub>V</sub>7.1 and KCNE1 is essential for normal repolarization and is compromised in short QT syndrome 2 (K<sub>V</sub>7.1-A287T). Rothenberg I HeartRhythm case reports 2016 PMID: 28491751
Exome Analyses of Long QT Syndrome Reveal Candidate Pathogenic Mutations in Calmodulin-Interacting Genes. Shigemizu D PloS one 2015 PMID: 26132555
Cellular mechanisms of mutations in Kv7.1: auditory functions in Jervell and Lange-Nielsen syndrome vs. Romano-Ward syndrome. Mousavi Nik A Frontiers in cellular neuroscience 2015 PMID: 25705178
A high-risk patient with long-QT syndrome with no response to cardioselective beta-blockers. Toyota N Heart and vessels 2015 PMID: 25028166
High-risk long QT syndrome mutations in the Kv7.1 (KCNQ1) pore disrupt the molecular basis for rapid K(+) permeation. Burgess DE Biochemistry 2012 PMID: 23092362
Paralogous annotation of disease-causing variants in long QT syndrome genes. Ware JS Human mutation 2012 PMID: 22581653
Genotype- and mutation site-specific QT adaptation during exercise, recovery, and postural changes in children with long-QT syndrome. Aziz PF Circulation. Arrhythmia and electrophysiology 2011 PMID: 21956039
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
Identification of a novel KCNQ1 mutation associated with both Jervell and Lange-Nielsen and Romano-Ward forms of long QT syndrome in a Chinese family. Zhang S BMC medical genetics 2008 PMID: 18400097
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

Text-mined citations for rs199472755...

Help
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 08, 2021