NM_000219.6(KCNE1):c.253G>A (p.Asp85Asn) AND Long QT syndrome 5

Germline classification:: Likely benign; risk factor (3 submissions)
Last evaluated:: Jun 8, 2017
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:: RCV000709727.16

Allele description [Variation Report for NM_000219.6(KCNE1):c.253G>A (p.Asp85Asn)]

NM_000219.6(KCNE1):c.253G>A (p.Asp85Asn)

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.253G>A (p.Asp85Asn)

HGVS:

NC_000021.9:g.34449382C>T
NG_009091.1:g.66934G>A
NM_000219.6:c.253G>AMANE SELECT
NM_001127668.4:c.253G>A
NM_001127669.4:c.253G>A
NM_001127670.4:c.253G>A
NM_001270402.3:c.253G>A
NM_001270403.2:c.253G>A
NM_001270404.3:c.253G>A
NM_001270405.3:c.253G>A
NP_000210.2:p.Asp85Asn
NP_001121140.1:p.Asp85Asn
NP_001121141.1:p.Asp85Asn
NP_001121142.1:p.Asp85Asn
NP_001121142.1:p.Asp85Asn
NP_001257331.1:p.Asp85Asn
NP_001257332.1:p.Asp85Asn
NP_001257333.1:p.Asp85Asn
NP_001257334.1:p.Asp85Asn
NP_001257334.1:p.Asp85Asn
LRG_290t1:c.253G>A
LRG_290:g.66934G>A
NC_000021.8:g.35821680C>T
NM_000219.3:c.253G>A
NM_000219.4:c.253G>A
NM_000219.5:c.253G>A
NM_001127670.3:c.253G>A
NM_001270402.1:c.253G>A
NM_001270405.2:c.253G>A
P15382:p.Asp85Asn
c.253G>A

Protein change:

D85N; ASP85ASN

Links:

UniProtKB: P15382#VAR_008902; OMIM: 176261.0005; dbSNP: rs1805128

NCBI 1000 Genomes Browser:

rs1805128

Molecular consequence:

NM_000219.6:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127668.4:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127669.4:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127670.4:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270402.3:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270403.2:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270404.3:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270405.3:c.253G>A - 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:: Long QT syndrome 5 (LQT5)
Identifiers:: MONDO: MONDO:0013372; MedGen: C1867904; Orphanet: 101016; Orphanet: 768; OMIM: 613695

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000435787	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Likely benign (Apr 27, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 14760488, 19695459 Citation Link,
SCV000839964	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	risk factor (Jun 8, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005393542	Roden Lab, Vanderbilt University Medical Center	no classification provided	not provided	not applicable	in vitro	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000435787

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Likely benign
(Apr 27, 2017)

germline

clinical testing

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

Citation Link,

SCV000839964

Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

risk factor
(Jun 8, 2017)

germline

clinical testing

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

SCV005393542

Roden Lab, Vanderbilt University Medical Center

no classification provided

not provided

not applicable

in vitro

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	not applicable	not applicable	not provided	not provided	not provided	not provided	not provided	in vitro

Citations

PubMed

Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients.

Paulussen AD, Gilissen RA, Armstrong M, Doevendans PA, Verhasselt P, Smeets HJ, Schulze-Bahr E, Haverkamp W, Breithardt G, Cohen N, Aerssens J.

J Mol Med (Berl). 2004 Mar;82(3):182-8. Epub 2004 Feb 4.

PubMed [citation]

PMID:: 14760488

D85N, a KCNE1 polymorphism, is a disease-causing gene variant in long QT syndrome.

Nishio Y, Makiyama T, Itoh H, Sakaguchi T, Ohno S, Gong YZ, Yamamoto S, Ozawa T, Ding WG, Toyoda F, Kawamura M, Akao M, Matsuura H, Kimura T, Kita T, Horie M.

J Am Coll Cardiol. 2009 Aug 25;54(9):812-9. doi: 10.1016/j.jacc.2009.06.005.

PubMed [citation]

PMID:: 19695459

See all PubMed Citations (4)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000435787.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV000839964.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This c.253G>A (p.D85N) variant (rs1805128) in the KCNE1 gene is a potassium channel susceptibility allele for with diLQTS, defined as documented torsades de pointes during treatment with a QT-prolonging drug [PMID 22100668, 24400172, 22999324, 14760488, 21244686, 17161064]. The variant has also been associated with longer QT [PMID 16132053]. A previous study has shown to predict diLQTS with an odds ratio of 9.0 (95% confidence interval, 3.5Ã¢â‚¬â€œ22.9) [PMID 22100668]. This variant is considered a risk allele for drug induced long QT.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Roden Lab, Vanderbilt University Medical Center, SCV005393542.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	in vitro	PubMed (1)

Description

Functional evidence assertions were derived from functional fitness scores.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not applicable	not applicable	not provided	not provided	discovery		not provided	not provided	not provided	not provided

Last Updated: Jan 19, 2025

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