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NM_000218.3(KCNQ1):c.691C>T (p.Arg231Cys) AND Cardiac arrhythmia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 8, 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:
RCV003591647.1

Allele description [Variation Report for NM_000218.3(KCNQ1):c.691C>T (p.Arg231Cys)]

NM_000218.3(KCNQ1):c.691C>T (p.Arg231Cys)

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.691C>T (p.Arg231Cys)
Other names:
p.R231C:CGC>TGC
HGVS:
  • NC_000011.10:g.2572020C>T
  • NG_008935.1:g.132030C>T
  • NM_000218.3:c.691C>TMANE SELECT
  • NM_001406836.1:c.691C>T
  • NM_001406837.1:c.421C>T
  • NM_181798.2:c.310C>T
  • NP_000209.2:p.Arg231Cys
  • NP_000209.2:p.Arg231Cys
  • NP_001393765.1:p.Arg231Cys
  • NP_001393766.1:p.Arg141Cys
  • NP_861463.1:p.Arg104Cys
  • NP_861463.1:p.Arg104Cys
  • LRG_287t1:c.691C>T
  • LRG_287t2:c.310C>T
  • LRG_287:g.132030C>T
  • LRG_287p1:p.Arg231Cys
  • LRG_287p2:p.Arg104Cys
  • NC_000011.9:g.2593250C>T
  • NM_000218.2:c.691C>T
  • NM_181798.1:c.310C>T
  • NR_040711.2:n.584C>T
  • P51787:p.Arg231Cys
Protein change:
R104C
Links:
UniProtKB: P51787#VAR_074956; dbSNP: rs199473457
NCBI 1000 Genomes Browser:
rs199473457
Molecular consequence:
  • NM_000218.3:c.691C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406836.1:c.691C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406837.1:c.421C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.2:c.310C>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004358384Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Aug 8, 2023) 		germlineclinical testing

PubMed (13)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Long QT syndrome in neonates: conduction disorders associated with HERG mutations and sinus bradycardia with KCNQ1 mutations.

Lupoglazoff JM, Denjoy I, Villain E, Fressart V, Simon F, Bozio A, Berthet M, Benammar N, Hainque B, Guicheney P.

J Am Coll Cardiol. 2004 Mar 3;43(5):826-30.

PubMed [citation]
PMID:
14998624

Four potassium channel mutations account for 73% of the genetic spectrum underlying long-QT syndrome (LQTS) and provide evidence for a strong founder effect in Finland.

Fodstad H, Swan H, Laitinen P, Piippo K, Paavonen K, Viitasalo M, Toivonen L, Kontula K.

Ann Med. 2004;36 Suppl 1:53-63.

PubMed [citation]
PMID:
15176425
See all PubMed Citations (13)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV004358384.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (13)

Description

This missense variant replaces arginine with cysteine at codon 231 of the KCNQ1 protein. This variant is found within a highly conserved region of the transmembrane domain S4 (a.a. 226-248). Rare nontruncating 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 causes constitutive channel activation and reduced current density after pulses relative to wildtype (PMID: 19843919, 20850564, 22509038, 33600800). This variant has been reported in over ten unrelated individuals affected with long QT syndrome and five individuals from two families affected with atrial fibrillation (PMID: 14998624, 15176425, 16922724, 19716085, 19843919, 20850564, 23193492, 36102233, 35911527). This variant has been reported to be a de novo occurrence in one of the probands (PMID: 14998624). It has been shown that this variant segregates with disease in multiple individuals from at least three of these families (PMID: 20850564, 23193492). This variant has been identified in 1/31342 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 20, 2024