NM_000218.3(KCNQ1):c.1552C>G (p.Arg518Gly) AND Long QT syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 16, 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:: RCV000045995.13

Allele description [Variation Report for NM_000218.3(KCNQ1):c.1552C>G (p.Arg518Gly)]

NM_000218.3(KCNQ1):c.1552C>G (p.Arg518Gly)

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.1552C>G (p.Arg518Gly)

HGVS:

NC_000011.10:g.2768881C>G
NG_008935.1:g.328891C>G
NM_000218.3:c.1552C>GMANE SELECT
NM_001406836.1:c.1456C>G
NM_001406837.1:c.1282C>G
NM_001406838.1:c.1012C>G
NM_181798.2:c.1171C>G
NP_000209.2:p.Arg518Gly
NP_000209.2:p.Arg518Gly
NP_001393765.1:p.Arg486Gly
NP_001393766.1:p.Arg428Gly
NP_001393767.1:p.Arg338Gly
NP_861463.1:p.Arg391Gly
NP_861463.1:p.Arg391Gly
LRG_287t1:c.1552C>G
LRG_287t2:c.1171C>G
LRG_287:g.328891C>G
LRG_287p1:p.Arg518Gly
LRG_287p2:p.Arg391Gly
NC_000011.9:g.2790111C>G
NM_000218.2:c.1552C>G
NM_181798.1:c.1171C>G
NR_040711.2:n.1445C>G
P51787:p.Arg518Gly

Protein change:

R338G

Links:

UniProtKB: P51787#VAR_075009; dbSNP: rs17215500

NCBI 1000 Genomes Browser:

rs17215500

Molecular consequence:

NM_000218.3:c.1552C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406836.1:c.1456C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406837.1:c.1282C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406838.1:c.1012C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_181798.2:c.1171C>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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HIBCH [Dermochelys coriacea]
HIBCH [Dermochelys coriacea]
Gene ID:119863261

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000074008	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 16, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16414944, 21511995, 24363352, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000074008

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 16, 2023)

germline

clinical testing

PubMed (4)
[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

Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice.

Napolitano C, Priori SG, Schwartz PJ, Bloise R, Ronchetti E, Nastoli J, Bottelli G, Cerrone M, Leonardi S.

JAMA. 2005 Dec 21;294(23):2975-80.

PubMed [citation]

PMID:: 16414944

Detection of extra components of T wave by independent component analysis in congenital long-QT syndrome.

Horigome H, Ishikawa Y, Shiono J, Iwamoto M, Sumitomo N, Yoshinaga M.

Circ Arrhythm Electrophysiol. 2011 Aug;4(4):456-64. doi: 10.1161/CIRCEP.110.958827. Epub 2011 Apr 21. Erratum in: Circ Arrhythm Electrophysiol. 2011 Oct;4(5):e71.

PubMed [citation]

PMID:: 21511995

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000074008.11

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

Description

This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 518 of the KCNQ1 protein (p.Arg518Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of long QT syndrome (PMID: 16414944, 21511995, 24363352; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 52991). 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. 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: Sep 29, 2024

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