U.S. flag

An official website of the United States government

NM_000219.6(KCNE1):c.226G>A (p.Asp76Asn) AND Long QT syndrome

Germline classification:
Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:
Jan 9, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000471399.23

Allele description [Variation Report for NM_000219.6(KCNE1):c.226G>A (p.Asp76Asn)]

NM_000219.6(KCNE1):c.226G>A (p.Asp76Asn)

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.226G>A (p.Asp76Asn)
HGVS:
  • NC_000021.9:g.34449409C>T
  • NG_009091.1:g.66907G>A
  • NM_000219.6:c.226G>AMANE SELECT
  • NM_001127668.4:c.226G>A
  • NM_001127669.4:c.226G>A
  • NM_001127670.4:c.226G>A
  • NM_001270402.3:c.226G>A
  • NM_001270403.2:c.226G>A
  • NM_001270404.3:c.226G>A
  • NM_001270405.3:c.226G>A
  • NP_000210.2:p.Asp76Asn
  • NP_001121140.1:p.Asp76Asn
  • NP_001121141.1:p.Asp76Asn
  • NP_001121142.1:p.Asp76Asn
  • NP_001121142.1:p.Asp76Asn
  • NP_001257331.1:p.Asp76Asn
  • NP_001257332.1:p.Asp76Asn
  • NP_001257333.1:p.Asp76Asn
  • NP_001257334.1:p.Asp76Asn
  • NP_001257334.1:p.Asp76Asn
  • LRG_290t1:c.226G>A
  • LRG_290:g.66907G>A
  • NC_000021.8:g.35821707C>T
  • NM_000219.3:c.226G>A
  • NM_000219.4:c.226G>A
  • NM_000219.5:c.226G>A
  • NM_001127670.3:c.226G>A
  • NM_001270402.2:c.226G>A
  • NM_001270405.2:c.226G>A
  • P15382:p.Asp76Asn
Protein change:
D76N; ASP76ASN
Links:
UniProtKB: P15382#VAR_008901; OMIM: 176261.0003; dbSNP: rs74315445
NCBI 1000 Genomes Browser:
rs74315445
Molecular consequence:
  • NM_000219.6:c.226G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127668.4:c.226G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127669.4:c.226G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127670.4:c.226G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270402.3:c.226G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270403.2:c.226G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270404.3:c.226G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270405.3:c.226G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Long QT syndrome (LQTS)
Identifiers:
MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000549148Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 9, 2024) 		germlineclinical testing

PubMed (12)
[See all records that cite these PMIDs]

SCV000987324Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Dec 22, 2016) 		germlineclinical testing

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

SCV004021977Dept of Medical Biology, Uskudar University
criteria provided, single submitter

(Dept of Medical Biology Variant Classification)		Likely pathogenic
(Jan 8, 2024) 		paternalresearch

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
Turkishpaternalyes1not providednot providednot providednot providedresearch

Citations

PubMed

KCNE1 mutations cause jervell and Lange-Nielsen syndrome.

Schulze-Bahr E, Wang Q, Wedekind H, Haverkamp W, Chen Q, Sun Y, Rubie C, Hördt M, Towbin JA, Borggrefe M, Assmann G, Qu X, Somberg JC, Breithardt G, Oberti C, Funke H.

Nat Genet. 1997 Nov;17(3):267-8. No abstract available.

PubMed [citation]
PMID:
9354783

Mutation of the gene for IsK associated with both Jervell and Lange-Nielsen and Romano-Ward forms of Long-QT syndrome.

Duggal P, Vesely MR, Wattanasirichaigoon D, Villafane J, Kaushik V, Beggs AH.

Circulation. 1998 Jan 20;97(2):142-6.

PubMed [citation]
PMID:
9445165
See all PubMed Citations (13)

Details of each submission

From Invitae, SCV000549148.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (12)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 76 of the KCNE1 protein (p.Asp76Asn). This variant is present in population databases (rs74315445, gnomAD 0.01%). This missense change has been observed in individual(s) with Jervell and Lange-Nielsen syndrome (JLNS) and long QT syndrome (PMID: 9354783, 9354802, 9445165, 19716085, 24561134, 24606995). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 13477). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KCNE1 protein function. Experimental studies have shown that this missense change affects KCNE1 function (PMID: 9354802, 10400998, 10428953, 11874988, 12566567, 24400172). For these reasons, this variant has been classified as Pathogenic.

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

From Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute, SCV000987324.1

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

From Dept of Medical Biology, Uskudar University, SCV004021977.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Turkish1not providednot providedresearchnot provided

Description

Criteria: PS3_Moderate, PM1, PP1, PP3

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

Last Updated: Apr 15, 2024