NM_000218.3(KCNQ1):c.613G>A (p.Val205Met) AND Congenital long QT syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 7, 2017
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:: RCV000119056.6

Allele description [Variation Report for NM_000218.3(KCNQ1):c.613G>A (p.Val205Met)]

NM_000218.3(KCNQ1):c.613G>A (p.Val205Met)

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.613G>A (p.Val205Met)

Other names:

KCNQ1 V205M; p.V205M:GTG>ATG

HGVS:

NC_000011.10:g.2571333G>A
NG_008935.1:g.131343G>A
NM_000218.3:c.613G>AMANE SELECT
NM_001406836.1:c.613G>A
NM_001406837.1:c.343G>A
NM_181798.2:c.232G>A
NP_000209.2:p.Val205Met
NP_000209.2:p.Val205Met
NP_001393765.1:p.Val205Met
NP_001393766.1:p.Val115Met
NP_861463.1:p.Val78Met
NP_861463.1:p.Val78Met
LRG_287t1:c.613G>A
LRG_287t2:c.232G>A
LRG_287:g.131343G>A
LRG_287p1:p.Val205Met
LRG_287p2:p.Val78Met
NC_000011.9:g.2592563G>A
NM_000218.2:c.613G>A
NM_181798.1:c.232G>A
NP_000209.2:p.V205M
NR_040711.2:n.506G>A

Protein change:

V115M; VAL205MET

Links:

OMIM: 607542.0040; dbSNP: rs151344631

NCBI 1000 Genomes Browser:

rs151344631

Molecular consequence:

NM_000218.3:c.613G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406836.1:c.613G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406837.1:c.343G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_181798.2:c.232G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Congenital long QT syndrome (RWS)
Synonyms:: Familial long QT syndrome; Romano-Ward syndrome; Ventricular fibrillation with prolonged QT interval
Identifiers:: MONDO: MONDO:0019171; MedGen: C1141890; Orphanet: 768; OMIM: PS192500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000089242	Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	no classification provided	not provided	germline	literature only	PubMed (4) [See all records that cite these PMIDs] 18580685, 20421371, 22378279, 22581653
SCV000711083	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Aug 7, 2017)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23844633, 25444851, 18580685, 20421371, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000089242

Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust

no classification provided

not provided

germline

literature only

PubMed (4)
[See all records that cite these PMIDs]

SCV000711083

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Aug 7, 2017)

germline

clinical testing

PubMed (5)
[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	not provided	1	1	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

High prevalence of genetic variants previously associated with LQT syndrome in new exome data.

Refsgaard L, Holst AG, Sadjadieh G, Haunsø S, Nielsen JB, Olesen MS.

Eur J Hum Genet. 2012 Aug;20(8):905-8. doi: 10.1038/ejhg.2012.23. Epub 2012 Feb 29.

PubMed [citation]

PMID:: 22378279
PMCID:: PMC3400735

Paralogous annotation of disease-causing variants in long QT syndrome genes.

Ware JS, Walsh R, Cunningham F, Birney E, Cook SA.

Hum Mutat. 2012 Aug;33(8):1188-1191. doi: 10.1002/humu.22114. Epub 2012 Jun 7.

PubMed [citation]

PMID:: 22581653
PMCID:: PMC4640174

See all PubMed Citations (7)

Details of each submission

From Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust, SCV000089242.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (4)

Description

This variant has been reported as associated with Long QT syndrome in the following publications (PMID:18580685;PMID:20421371;PMID:22378279). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

#	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

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000711083.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (5)

Description

The p.Val205Met variant in KCNQ1 has been reported in 2 individuals with long QT syndrome and segregated with disease in at least 10 affected relatives from bot h families (Arbour 2008). Additionally, four individuals have been reported to b e homozygous for this variant and present with a clinically more severe phenotyp e that did not include hearing loss (Jackson 2014). This variant has also been r eported by other clinical laboratories in ClinVar (variation ID: 3725) and has b een identified in 1/126300 European chromosomes by the Genome Aggregation Databa se (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs151344631). In vitro func tional studies provide evidence that the p.Val205Met variant may impact protein function (Arbour 2008, Eldstrom 2010, Eldstrom 2015). In summary, this variant m eets criteria to be classified as pathogenic for long QT syndrome in an autosoma l dominant manner based upon segregation studies and functional evidence.

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

Last Updated: Oct 20, 2024

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