NM_000218.3(KCNQ1):c.520C>T (p.Arg174Cys) AND Arrhythmia

Clinical significance:Likely pathogenic (Last evaluated: Nov 4, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001184215.1

Allele description [Variation Report for NM_000218.3(KCNQ1):c.520C>T (p.Arg174Cys)]

NM_000218.3(KCNQ1):c.520C>T (p.Arg174Cys)

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.520C>T (p.Arg174Cys)
Other names:
p.R174C:CGC>TGC
HGVS:
  • NC_000011.10:g.2570670C>T
  • NG_008935.1:g.130680C>T
  • NM_000218.2:c.520C>T
  • NM_000218.3:c.520C>TMANE SELECT
  • NM_181798.1:c.139C>T
  • NP_000209.2:p.Arg174Cys
  • NP_000209.2:p.Arg174Cys
  • NP_861463.1:p.Arg47Cys
  • LRG_287t1:c.520C>T
  • LRG_287t2:c.139C>T
  • LRG_287:g.130680C>T
  • LRG_287p1:p.Arg174Cys
  • LRG_287p2:p.Arg47Cys
  • NC_000011.9:g.2591900C>T
  • P51787:p.Arg174Cys
Protein change:
R174C
Links:
UniProtKB: P51787#VAR_001517; dbSNP: rs199472696
NCBI 1000 Genomes Browser:
rs199472696
Molecular consequence:
  • NM_000218.2:c.520C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000218.3:c.520C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.1:c.139C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Arrhythmia
Identifiers:
EFO: EFO_0004269; MedGen: C0855329; Human Phenotype Ontology: HP:0011675

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001350155Color Health, Inccriteria provided, single submitter
Likely pathogenic
(Nov 4, 2018)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Description

This missense variant is located in the cytoplasmic linker between transmembrane domains S2 and S3 of the KCNQ1 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. Experimental functional studies have shown that this variant adversely affects KCNQ1 channel function (PMID: 9312006, 19934648, 29449639). This variant has been reported in multiple unrelated individuals affected with long QT syndrome (PMID: 11668638, 23130128, 27251404, 29449639) and in individuals referred for long QT syndrome testing (PMID: 15840476, 19716085). This variant has also been reported in the homozygous and compound heterozygous state in individuals affected with Jervell and Lange-Nielsen syndrome (PMID: 23392653, 29037160). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on available evidence, this variant is classified as Likely Pathogenic.

SCV001350155

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Color Health, Inc, SCV001350155.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 20, 2021

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