NM_000218.3(KCNQ1):c.332A>G (p.Tyr111Cys) AND Long QT syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 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:: RCV002513652.2

Allele description [Variation Report for NM_000218.3(KCNQ1):c.332A>G (p.Tyr111Cys)]

NM_000218.3(KCNQ1):c.332A>G (p.Tyr111Cys)

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.332A>G (p.Tyr111Cys)

Other names:

p.Y111C:TAC>TGC

HGVS:

NC_000011.10:g.2445430A>G
NG_008935.1:g.5440A>G
NM_000218.3:c.332A>GMANE SELECT
NP_000209.2:p.Tyr111Cys
NP_000209.2:p.Tyr111Cys
LRG_287t1:c.332A>G
LRG_287:g.5440A>G
LRG_287p1:p.Tyr111Cys
NC_000011.9:g.2466660A>G
NM_000218.2:c.332A>G
P51787:p.Tyr111Cys

Protein change:

Y111C

Links:

UniProtKB: P51787#VAR_009918; dbSNP: rs199472678

NCBI 1000 Genomes Browser:

rs199472678

Molecular consequence:

NM_000218.3:c.332A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003439745	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 30, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 10973849, 20031635, 21129503, 22539601, 17053194, 19114714, 29532034, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003439745

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 30, 2023)

germline

clinical testing

PubMed (8)
[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

Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.

Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT.

Circulation. 2000 Sep 5;102(10):1178-85.

PubMed [citation]

PMID:: 10973849

Low incidence of sudden cardiac death in a Swedish Y111C type 1 long-QT syndrome population.

Winbo A, Diamant UB, Stattin EL, Jensen SM, Rydberg A.

Circ Cardiovasc Genet. 2009 Dec;2(6):558-64. doi: 10.1161/CIRCGENETICS.108.825547. Epub 2009 Sep 14.

PubMed [citation]

PMID:: 20031635

See all PubMed Citations (8)

Details of each submission

From Invitae, SCV003439745.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 111 of the KCNQ1 protein (p.Tyr111Cys). This variant is present in population databases (rs199472678, gnomAD 0.002%). This missense change has been observed in individual(s) with Jervell and Lange-Nielsen syndrome and/or long QT syndrome (PMID: 10973849, 20031635, 21129503, 22539601). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 53035). 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. Experimental studies have shown that this missense change affects KCNQ1 function (PMID: 17053194, 19114714, 29532034). 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

ClinVar

Relating variation to medicine