NM_000219.6(KCNE1):c.292C>T (p.Arg98Trp) AND Cardiovascular phenotype

Clinical significance:Likely pathogenic (Last evaluated: Jan 22, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000619552.2

Allele description [Variation Report for NM_000219.6(KCNE1):c.292C>T (p.Arg98Trp)]

NM_000219.6(KCNE1):c.292C>T (p.Arg98Trp)

Gene:
KCNE1:potassium voltage-gated channel subfamily E regulatory subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
21q22.12
Genomic location:
Preferred name:
NM_000219.6(KCNE1):c.292C>T (p.Arg98Trp)
HGVS:
  • NC_000021.9:g.34449343G>A
  • NG_009091.1:g.66973C>T
  • NM_000219.6:c.292C>TMANE SELECT
  • NM_001127668.3:c.292C>T
  • NM_001127669.4:c.292C>T
  • NM_001127670.3:c.292C>T
  • NM_001270402.2:c.292C>T
  • NM_001270403.2:c.292C>T
  • NM_001270404.2:c.292C>T
  • NM_001270405.2:c.292C>T
  • NP_000210.2:p.Arg98Trp
  • NP_001121140.1:p.Arg98Trp
  • NP_001121141.1:p.Arg98Trp
  • NP_001121142.1:p.Arg98Trp
  • NP_001257331.1:p.Arg98Trp
  • NP_001257332.1:p.Arg98Trp
  • NP_001257333.1:p.Arg98Trp
  • NP_001257334.1:p.Arg98Trp
  • LRG_290t1:c.292C>T
  • LRG_290:g.66973C>T
  • NC_000021.8:g.35821641G>A
  • NM_000219.3:c.292C>T
  • NM_000219.5:c.292C>T
  • P15382:p.Arg98Trp
Protein change:
R98W
Links:
UniProtKB: P15382#VAR_009907; dbSNP: rs199473362
NCBI 1000 Genomes Browser:
rs199473362
Molecular consequence:
  • NM_000219.6:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127668.3:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127669.4:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127670.3:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270402.2:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270403.2:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270404.2:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270405.2:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000737536Ambry Geneticscriteria provided, single submitter
Likely pathogenic
(Jan 22, 2020)
germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical 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

Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome.

Millat G, Chevalier P, Restier-Miron L, Da Costa A, Bouvagnet P, Kugener B, Fayol L, Gonzàlez Armengod C, Oddou B, Chanavat V, Froidefond E, Perraudin R, Rousson R, Rodriguez-Lafrasse C.

Clin Genet. 2006 Sep;70(3):214-27.

PubMed [citation]
PMID:
16922724
See all PubMed Citations (11)

Details of each submission

From Ambry Genetics, SCV000737536.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (11)

Description

The p.R98W variant (also known as c.292C>T), located in coding exon 1 of the KCNE1 gene, results from a C to T substitution at nucleotide position 292. The arginine at codon 98 is replaced by tryptophan, an amino acid with dissimilar properties. In long QT syndrome cohorts, this variant has been described in patients with QT interval prolongation, repolarization abnormalities and/or syncope, aborted cardiac arrest, or sudden death upon physical exertion (Splawski I et al. Circulation. 2000;102(10):1178-85; Millat G et al. Clin Genet. 2006;70(3):214-27; Ohno S et al. Heart Rhythm. 2007;4(3):332-40; Skinner JR et al. Heart Rhythm. 2011;8(3):412-9). In one family with epilepsy and long QT syndrome, this variant did not segregate with disease and a KCNQ1 exon 2 deletion did segregate with disease (Coll M et al. PLoS ONE, 2017 Dec;12:e0189618). In studies using in vitro functional analyses, this variant adversely affected the voltage-gated potassium ion channel, resulting in decreased current amplitude, a positive shift of the voltage dependence of activation threshold, and accelerated channel deactivation (Ohno S et al. Heart Rhythm. 2007;4(3):332-40; Harmer SC et al. Am J Physiol.,Cell Physiol. 2010;298(2):C263-73). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the majority of available evidence to date, this variant is likely to be pathogenic. <br />

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Oct 6, 2021

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