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NM_000219.6(KCNE1):c.137A>G (p.Tyr46Cys) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 16, 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:
RCV002385950.3

Allele description [Variation Report for NM_000219.6(KCNE1):c.137A>G (p.Tyr46Cys)]

NM_000219.6(KCNE1):c.137A>G (p.Tyr46Cys)

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.137A>G (p.Tyr46Cys)
HGVS:
  • NC_000021.9:g.34449498T>C
  • NG_009091.1:g.66818A>G
  • NM_000219.6:c.137A>GMANE SELECT
  • NM_001127668.4:c.137A>G
  • NM_001127669.4:c.137A>G
  • NM_001127670.4:c.137A>G
  • NM_001270402.3:c.137A>G
  • NM_001270403.2:c.137A>G
  • NM_001270404.3:c.137A>G
  • NM_001270405.3:c.137A>G
  • NP_000210.2:p.Tyr46Cys
  • NP_001121140.1:p.Tyr46Cys
  • NP_001121141.1:p.Tyr46Cys
  • NP_001121142.1:p.Tyr46Cys
  • NP_001257331.1:p.Tyr46Cys
  • NP_001257332.1:p.Tyr46Cys
  • NP_001257333.1:p.Tyr46Cys
  • NP_001257334.1:p.Tyr46Cys
  • LRG_290t1:c.137A>G
  • LRG_290:g.66818A>G
  • NC_000021.8:g.35821796T>C
  • NM_000219.3:c.137A>G
Protein change:
Y46C
Links:
dbSNP: rs1402178514
NCBI 1000 Genomes Browser:
rs1402178514
Molecular consequence:
  • NM_000219.6:c.137A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127668.4:c.137A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127669.4:c.137A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127670.4:c.137A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270402.3:c.137A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270403.2:c.137A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270404.3:c.137A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270405.3:c.137A>G - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
Effect on ion channel function [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0001] - Comment(s)

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
SCV002696444Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Uncertain significance
(Aug 16, 2023)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

Probing the structural basis for differential KCNQ1 modulation by KCNE1 and KCNE2.

Wang Y, Zhang M, Xu Y, Jiang M, Zankov DP, Cui M, Tseng GN.

J Gen Physiol. 2012 Dec;140(6):653-69. doi: 10.1085/jgp.201210847.

PubMed [citation]
PMID:
23183700
PMCID:
PMC3514736

An International Multicenter Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition.

Roberts JD, Asaki SY, Mazzanti A, Bos JM, Tuleta I, Muir AR, Crotti L, Krahn AD, Kutyifa V, Shoemaker MB, Johnsrude CL, Aiba T, Marcondes L, Baban A, Udupa S, Dechert B, Fischbach P, Knight LM, Vittinghoff E, Kukavica D, Stallmeyer B, Giudicessi JR, et al.

Circulation. 2020 Feb 11;141(6):429-439. doi: 10.1161/CIRCULATIONAHA.119.043114. Epub 2020 Jan 16.

PubMed [citation]
PMID:
31941373
PMCID:
PMC7035205

Details of each submission

From Ambry Genetics, SCV002696444.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The p.Y46C variant (also known as c.137A>G), located in coding exon 1 of the KCNE1 gene, results from an A to G substitution at nucleotide position 137. The tyrosine at codon 46 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in a long QT syndrome cohort; however, clinical details were limited (Roberts JD et al. Circulation, 2020 Feb;141:429-439). Limited functional studies have suggested this alteration may impact current amplitudes and pore conductance (Wang Y et al. J. Gen. Physiol., 2012 Dec;140:653-69). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Nov 10, 2024