NM_000218.3(KCNQ1):c.1031C>T (p.Ala344Val) AND Cardiac arrhythmia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 3, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003591636.2

Allele description [Variation Report for NM_000218.3(KCNQ1):c.1031C>T (p.Ala344Val)]

NM_000218.3(KCNQ1):c.1031C>T (p.Ala344Val)

Gene:

KCNQ1:potassium voltage-gated channel subfamily Q member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_000218.3(KCNQ1):c.1031C>T (p.Ala344Val)

HGVS:

NC_000011.10:g.2583544C>T
NG_008935.1:g.143554C>T
NM_000218.3:c.1031C>TMANE SELECT
NM_001406836.1:c.1031C>T
NM_001406837.1:c.761C>T
NM_001406838.1:c.587C>T
NM_181798.2:c.650C>T
NP_000209.2:p.Ala344Val
NP_000209.2:p.Ala344Val
NP_001393765.1:p.Ala344Val
NP_001393766.1:p.Ala254Val
NP_001393767.1:p.Ala196Val
NP_861463.1:p.Ala217Val
NP_861463.1:p.Ala217Val
LRG_287t1:c.1031C>T
LRG_287t2:c.650C>T
LRG_287:g.143554C>T
LRG_287p1:p.Ala344Val
LRG_287p2:p.Ala217Val
NC_000011.9:g.2604774C>T
NM_000218.2:c.1031C>T
NM_181798.1:c.650C>T
NR_040711.2:n.924C>T
P51787:p.Ala344Val

Protein change:

A196V

Links:

UniProtKB: P51787#VAR_001541; dbSNP: rs199472763

NCBI 1000 Genomes Browser:

rs199472763

Molecular consequence:

NM_000218.3:c.1031C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406836.1:c.1031C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406837.1:c.761C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406838.1:c.587C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_181798.2:c.650C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiac arrhythmia
Synonyms:: Cardiac rhythm disease
Identifiers:: EFO: EFO_0004269; MONDO: MONDO:0007263; MedGen: C0003811; Human Phenotype Ontology: HP:0011675

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004358402	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 3, 2023)	germline	clinical testing	PubMed (16) [See all records that cite these PMIDs] 9386136, 15840476, 16931984, 19716085, 20851114, 24217263, 26669661, 27920829, 28438721, 28944242, 32015334, 32298319, 32893267, 34505893, 34884666, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004358402

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 3, 2023)

germline

clinical testing

PubMed (16)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome.

Donger C, Denjoy I, Berthet M, Neyroud N, Cruaud C, Bennaceur M, Chivoret G, Schwartz K, Coumel P, Guicheney P.

Circulation. 1997 Nov 4;96(9):2778-81.

PubMed [citation]

PMID:: 9386136

Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.

Tester DJ, Will ML, Haglund CM, Ackerman MJ.

Heart Rhythm. 2005 May;2(5):507-17.

PubMed [citation]

PMID:: 15840476

See all PubMed Citations (16)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV004358402.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (16)

Description

This missense variant replaces alanine with valine at codon 344 of the KCNQ1 protein. This variant is found within a highly conserved region in transmembrane domain S6 (a.a. 328-348). Rare non-truncating variants in this region have been shown to be significantly overrepresented in individuals with long QT syndrome (PMID: 32893267). Functional studies have shown that this variant affects gating properties and increases channel sensitivity to anesthetics (PMID: 16931984, 32015334 ). This variant has been reported in heterozygous state in over ten unrelated individuals affected with long QT syndrome (PMID: 9386136, 15840476, 19716085, 20851114, 24217263, 26669661, 27920829, 32298319, 32893267, 34505893, 34884666) and in homozygous state in at least three individuals affected with severe long QT syndrome without hearing loss (PMID: 28438721, 28944242). This variant has been report to be a de novo occurrence in a child with severe long QT syndrome in compound heterozygous state with p.Ala300Thr variant in the same gene (PMID: 34884666). This variant has also been observed in over twenty unaffected heterozygous individuals (PMID: 9386136, 28438721, 28944242, 34505893). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 29, 2025

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