NM_000218.3(KCNQ1):c.1571T>G (p.Val524Gly) AND Long QT syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 30, 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:: RCV000046000.13

Allele description

NM_000218.3(KCNQ1):c.1571T>G (p.Val524Gly)

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.1571T>G (p.Val524Gly)

Other names:

p.V524G:GTG>GGG

HGVS:

NC_000011.10:g.2768900T>G
NG_008935.1:g.328910T>G
NM_000218.3:c.1571T>GMANE SELECT
NM_001406836.1:c.1475T>G
NM_001406837.1:c.1301T>G
NM_001406838.1:c.1031T>G
NM_181798.2:c.1190T>G
NP_000209.2:p.Val524Gly
NP_000209.2:p.Val524Gly
NP_001393765.1:p.Val492Gly
NP_001393766.1:p.Val434Gly
NP_001393767.1:p.Val344Gly
NP_861463.1:p.Val397Gly
NP_861463.1:p.Val397Gly
LRG_287t1:c.1571T>G
LRG_287t2:c.1190T>G
LRG_287:g.328910T>G
LRG_287p1:p.Val524Gly
LRG_287p2:p.Val397Gly
NC_000011.9:g.2790130T>G
NM_000218.2:c.1571T>G
NM_181798.1:c.1190T>G
NR_040711.2:n.1464T>G
P51787:p.Val524Gly

Protein change:

V344G

Links:

UniProtKB: P51787#VAR_068315; dbSNP: rs199472790

NCBI 1000 Genomes Browser:

rs199472790

Molecular consequence:

NM_000218.3:c.1571T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406836.1:c.1475T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406837.1:c.1301T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406838.1:c.1031T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_181798.2:c.1190T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Long QT syndrome (LQTS)
Identifiers:: MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000074013	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 30, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 14678125, 15840476, 17470695, 22949429, 23392653, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000074013

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 30, 2023)

germline

clinical testing

PubMed (6)
[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

Location of mutation in the KCNQ1 and phenotypic presentation of long QT syndrome.

Zareba W, Moss AJ, Sheu G, Kaufman ES, Priori S, Vincent GM, Towbin JA, Benhorin J, Schwartz PJ, Napolitano C, Hall WJ, Keating MT, Qi M, Robinson J, Andrews ML; International LQTS Registry, University of Rochester, Rochester, New York..

J Cardiovasc Electrophysiol. 2003 Nov;14(11):1149-53.

PubMed [citation]

PMID:: 14678125

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 (6)

Details of each submission

From Invitae, SCV000074013.12

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 524 of the KCNQ1 protein (p.Val524Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant long QT syndrome (PMID: 14678125, 15840476, 17470695, 22949429). This variant has been reported in individual(s) with autosomal recessive long QT syndrome without hearing loss typically associated with autosomal recessive Jervell and Lange-Nielsen syndrome (PMID: 23392653); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 52994). 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%. For these reasons, this variant has been 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: May 1, 2024

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