NM_000219.6(KCNE1):c.292C>T (p.Arg98Trp) AND Long QT syndrome 5

Clinical significance:Pathogenic (Last evaluated: Jul 5, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000709726.1

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_001127668.4:c.292C>T
  • NM_001127669.4:c.292C>T
  • NM_001127670.4:c.292C>T
  • NM_001270402.3:c.292C>T
  • NM_001270403.2:c.292C>T
  • NM_001270404.3:c.292C>T
  • NM_001270405.2:c.292C>T
  • NM_001270405.3: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
  • NP_001257334.1:p.Arg98Trp
  • LRG_290t1:c.292C>T
  • LRG_290:g.66973C>T
  • NC_000021.8:g.35821641G>A
  • 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_001127668.4:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127669.4:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127670.4:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270402.3:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270403.2:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270404.3:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270405.2:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270405.3:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Long QT syndrome 5 (LQT5)
Identifiers:
MONDO: MONDO:0013372; MedGen: C1867904; Orphanet: 101016; Orphanet: 768; OMIM: 613695

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000839963Human Genome Sequencing Center Clinical Lab, Baylor College of Medicinecriteria provided, single submitter
Pathogenic
(Jul 5, 2017)
germlineclinical testing

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

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 Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV000839963.1

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

Description

This c.292C>T (p.Arg98Trp) variant in the KCNE1 gene has been reported in 6 individuals and one family from a cohort of 262 patients with long QT [PMID 10973849] and additional patients [PMID 16922724, 17341399]. Segregation of the variant with the disorder was observed in one additional family of 7 individuals, 2 of which were carrier for this variant [PMID 21070882]. Functional assays showed a modest effect of the variant on trafficking and current density [PMID 17341399]. This variant was reported in 2 heterozygous individuals from Europe and East-Asia (http://exac.broadinstitute.org/variant/21-35821641-G-A). Arginine at amino acid position 98 of the KCNE1 protein is highly conserved in mammals. While not validated for clinical use, computer-based algorithms SIFT and Polyphen-2 predict this p.Arg98Trp change to be deleterious. This variant thus classified as pathogenic.

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

Last Updated: Oct 24, 2021

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