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NM_181798.1(KCNQ1):c.49A>G (p.Thr17Ala)

Conflicting interpretations of pathogenicity​

Likely pathogenic(1);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
4 (Most recent: Sep 25, 2021)
Last evaluated:
May 20, 2020
Variation ID:
single nucleotide variant

NM_181798.1(KCNQ1):c.49A>G (p.Thr17Ala)

Allele ID
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
Genomic location
11: 2527971 (GRCh38) GRCh38 UCSC
11: 2549201 (GRCh37) GRCh37 UCSC
Nucleotide Protein Molecular
LRG_287t1:c.430A>G LRG_287p1:p.Thr144Ala
LRG_287t2:c.49A>G LRG_287p2:p.Thr17Ala
... more HGVS
Protein change
T144A, T17A
Other names
Canonical SPDI
Functional consequence
Global minor allele frequency (GMAF)

Allele frequency
ClinGen: CA007072
UniProtKB: P51787#VAR_074936
dbSNP: rs199473451

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 1 criteria provided, single submitter May 20, 2020 RCV000463475.6
Uncertain significance 1 criteria provided, single submitter Feb 19, 2020 RCV000489920.3
Uncertain significance 1 criteria provided, single submitter Jun 27, 2017 RCV000618499.1
not provided 1 no assertion provided - RCV000057675.3
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
1161 1427

Submitted interpretations and evidence

(Last evaluated)
Review status
(Assertion criteria)
Submitter Supporting information
Uncertain significance
(Jun 27, 2017)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000738071.3
Submitted: (Nov 30, 2020)
Evidence details
PubMed (4)
The p.T144A variant (also known as c.430A>G), located in coding exon 2 of the KCNQ1 gene, results from an A to G substitution at nucleotide … (more)
Likely pathogenic
(May 20, 2020)
criteria provided, single submitter
Method: clinical testing
Long QT syndrome
Allele origin: germline
Accession: SCV000543293.6
Submitted: (Jan 07, 2021)
Evidence details
PubMed (5)
This sequence change replaces threonine with alanine at codon 144 of the KCNQ1 protein (p.Thr144Ala). The threonine residue is highly conserved and there is a … (more)
Uncertain significance
(Feb 19, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
Accession: SCV000576622.4
Submitted: (Sep 25, 2021)
Evidence details
Reported independently and in conjunction with the R594P variant in the KCNQ1 gene in multiple unrelated individuals with LQTS (Zareba et al., 2003; Miller et … (more)
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: SCV000089194.3
Submitted: (Sep 22, 2016)
Evidence details
PubMed (5)
This variant has been reported as associated with Long QT syndrome in the following publications (PMID:14678125;PMID:17224687;PMID:19716085;PMID:17470695). This is a literature report, and does not necessarily … (more)

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 this variant

Title Author Journal Year Link
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
A conserved threonine in the S1-S2 loop of KV7.2 and K V7.3 channels regulates voltage-dependent activation. Füll Y Pflugers Archiv : European journal of physiology 2013 PMID: 23271449
Paralogous annotation of disease-causing variants in long QT syndrome genes. Ware JS Human mutation 2012 PMID: 22581653
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
Whole blood RNA offers a rapid, comprehensive approach to genetic diagnosis of cardiovascular diseases. Miller TE Genetics in medicine : official journal of the American College of Medical Genetics 2007 PMID: 17224687
Location of mutation in the KCNQ1 and phenotypic presentation of long QT syndrome. Zareba W Journal of cardiovascular electrophysiology 2003 PMID: 14678125

Text-mined citations for rs199473451...

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