This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PS3,PS4,PP5,BS1,BP6.
ClinVar Genomic variation as it relates to human health
NM_000219.6(KCNE1):c.253G>A (p.Asp85Asn)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(24)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Conflicting classifications of pathogenicity; other; risk factor
Uncertain significance(2); Benign(7); Likely benign(6)
Uncertain significance(2); Benign(7); Likely benign(6)
24
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000219.6(KCNE1):c.253G>A (p.Asp85Asn)
Variation ID: 13479 Accession: VCV000013479.72
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 21q22.12 21: 34449382 (GRCh38) [ NCBI UCSC ] 21: 35821680 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Nov 10, 2024 Aug 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000219.6:c.253G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000210.2:p.Asp85Asn missense NM_001127668.4:c.253G>A NP_001121140.1:p.Asp85Asn missense NM_001127669.4:c.253G>A NP_001121141.1:p.Asp85Asn missense NM_001127670.4:c.253G>A NP_001121142.1:p.Asp85Asn missense NM_001270402.3:c.253G>A NP_001257331.1:p.Asp85Asn missense NM_001270403.2:c.253G>A NP_001257332.1:p.Asp85Asn missense NM_001270404.3:c.253G>A NP_001257333.1:p.Asp85Asn missense NM_001270405.3:c.253G>A NP_001257334.1:p.Asp85Asn missense NC_000021.9:g.34449382C>T NC_000021.8:g.35821680C>T NG_009091.1:g.66934G>A LRG_290:g.66934G>A LRG_290t1:c.253G>A P15382:p.Asp85Asn - Protein change
- D85N
- Other names
- -
- Canonical SPDI
- NC_000021.9:34449381:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
Effect on ion channel function; Functional Epilepsy Nomenclature for Ion Channels [ FENICS-0001]This variant was studied in a multiplexed assay of variant effect (PMID 38816749). This variant had a mean functional score of 0.919 (0.797-1.041 confidence interval). This score is on a scale where the median nonsense variant had a score of 0 and the median synonymous variant had a score of 1. This score was determined to be "normal function". Calibration with control variants resulted in a recommended application of PS3 or BS3 at a maximum of moderate level for this assay. [submitted by Roden Lab, Vanderbilt University Medical Center]
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.00379 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
1000 Genomes Project 0.00379
The Genome Aggregation Database (gnomAD) 0.00841
Exome Aggregation Consortium (ExAC) 0.00916
The Genome Aggregation Database (gnomAD), exomes 0.00944
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| KCNE1 | - | - |
GRCh38 GRCh37 |
1261 | 1339 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| no classifications from unflagged records (1) |
no classifications from unflagged records
|
Feb 9, 2024 | RCV000014423.36 | |
| risk factor (1) |
no assertion criteria provided
|
Aug 1, 2006 | RCV000014422.12 | |
| Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Sep 25, 2023 | RCV000035353.28 | |
| Likely benign (1) |
criteria provided, single submitter
|
Jun 25, 2018 | RCV000247942.12 | |
| Benign; other (6) |
criteria provided, multiple submitters, no conflicts
|
Aug 1, 2024 | RCV000057858.48 | |
| Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Nov 1, 2022 | RCV000157255.31 | |
| Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Oct 15, 2018 | RCV000399257.17 | |
| Likely benign; risk factor (3) |
criteria provided, multiple submitters, no conflicts
|
Jun 8, 2017 | RCV000709727.16 | |
| Benign (1) |
criteria provided, single submitter
|
Apr 1, 2019 | RCV000852954.9 | |
| Likely benign; risk factor (2) |
criteria provided, multiple submitters, no conflicts
|
Mar 4, 2020 | RCV001195103.18 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Mar 30, 2021 | RCV003224097.8 | |
| click to load more click to collapse | ||||
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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|---|---|---|---|---|---|
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Uncertain significance
(Oct 15, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Jervell and Lange-Nielsen syndrome 2
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001369904.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in … (more)
This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PS3,PS4,PP5,BS1,BP6. (less)
|
|
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Benign
(Mar 03, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001899783.1
First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 19019189, 32429735, 31447099, 31918855, 30384889, 17266934, 29874177, 28798025, 28003625, 29625280, 29540472, 27509294, 14760488, 24400172, 24561134, 19695459, … (more)
This variant is associated with the following publications: (PMID: 19019189, 32429735, 31447099, 31918855, 30384889, 17266934, 29874177, 28798025, 28003625, 29625280, 29540472, 27509294, 14760488, 24400172, 24561134, 19695459, 22999324, 20823649, 25119684, 16823764, 23237912, 23631430, 22995991, 21712262, 16132053, 22378279, 15051636, 22100668, 21244686, 17161064) (less)
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Benign
(Nov 29, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000884042.6
First in ClinVar: Oct 09, 2016 Last updated: Feb 20, 2024 |
|
|
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Benign
(Jun 24, 2013)
|
criteria provided, single submitter
Method: research
|
Long QT syndrome
Affected status: unknown
Allele origin:
unknown
|
Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000050822.2 First in ClinVar: Jun 04, 2015 Last updated: Sep 14, 2015
Comments (2):
The study set was not selected for affection status in relation to any cancer. HGMD phenotype assertion is uncertain. Pathogenicity categories were based on literature … (more)
The study set was not selected for affection status in relation to any cancer. HGMD phenotype assertion is uncertain. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for details. (less)
Medical sequencing
|
Number of individuals with the variant: 24
|
|
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Likely benign
(Jun 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Romano-Ward Syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000435785.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
|
|
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other
(Jul 24, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
Accession: SCV000747999.1
First in ClinVar: Oct 09, 2016 Last updated: Oct 09, 2016 |
|
|
|
risk factor
(Jun 08, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Long QT syndrome 5
Affected status: unknown
Allele origin:
germline
|
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV000839964.1
First in ClinVar: Oct 14, 2018 Last updated: Oct 14, 2018 |
Comment:
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 … (more)
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, 3.5–22.9) [PMID 22100668]. This variant is considered a risk allele for drug induced long QT. (less)
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Benign
(Sep 21, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000335035.3
First in ClinVar: Dec 06, 2016 Last updated: May 03, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
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Benign
(Apr 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiomyopathy
Affected status: yes
Allele origin:
germline
|
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego
Accession: SCV000995701.1
First in ClinVar: Oct 12, 2019 Last updated: Oct 12, 2019 |
Number of individuals with the variant: 2
|
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Jervell and Lange-Nielsen syndrome 2
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000435786.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
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, … (more)
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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Long QT syndrome 5
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000435787.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
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, … (more)
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. (less)
|
|
|
risk factor
(Mar 04, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital long QT syndrome
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000059001.7
First in ClinVar: May 03, 2013 Last updated: Jul 04, 2020 |
Comment:
KCNE1 c.253G>A (p.Asp85Asn) has been associated with increased risk for long QT syndrome. This variant has been observed in multiple ethnic backgrounds with highest frequencies … (more)
KCNE1 c.253G>A (p.Asp85Asn) has been associated with increased risk for long QT syndrome. This variant has been observed in multiple ethnic backgrounds with highest frequencies in individuals of Ashkenazi Jewish ancestry (2.5%, Genome Aggregation Database (gnomAD); rs1805128) and is present in ClinVar (ID: 13479). Several studies have also reported an odds ratio of 4.2-8.9 for developing Long QT syndrome in heterozygous carriers of this variant (OR=8.88 [95% CI 3.26-24.17] Kaab 2011, OR=4.21 [95% CI 1.17-15.16] Gouas 2005). In vitro functional studies provide some evidence that this variant may impact protein function (Nishio 2009). In summary, this variant is a likely risk factor for Long QT syndrome. (less)
Number of individuals with the variant: 32
|
|
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Benign
(Dec 07, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Long QT syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000218636.10
First in ClinVar: Mar 29, 2015 Last updated: Jun 15, 2021 |
|
|
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Uncertain significance
(Mar 30, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Jervell and Lange-Nielsen syndrome 2
Long QT syndrome 5
Affected status: unknown
Allele origin:
germline
|
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV003920090.1
First in ClinVar: Apr 30, 2023 Last updated: Apr 30, 2023 |
Comment:
KCNE1 NM_000219.4 exon 4 p.Asp85Asn (c.253G>A): This variant has been reported in the literature in several individuals with LQTS and is reported to be overrepresented … (more)
KCNE1 NM_000219.4 exon 4 p.Asp85Asn (c.253G>A): This variant has been reported in the literature in several individuals with LQTS and is reported to be overrepresented in this patient population compared to control individuals (Westenskow 2004 PMID:15051636, Nishio 2009 PMID:19695459, Kaab 2012 PMID:22100668, Weeke 2014 PMID:24561134, Maltese 2017 PMID:28003625, Lane 2018 PMID:29625280). Several authors in the literature suggest that this variant may act as a risk allele or modifying allele (Gouas 2005 PMID:16132053, Lahtinen 2011 PMID:21244686, Weeke 2014 PMID:24561134, Lane 2018 PMID:29625280). However, this variant is also present in 2.5% (263/10368) of Ashkenazi Jewish alleles in the Genome Aggregation Database, including 5 homozygotes (https://gnomad.broadinstitute.org/variant/21-35821680-C-T), suggesting that it may be a benign polymorphism. This variant is present in ClinVar (Variation ID:13479). Evolutionary conservation and computational predictive tools for this variant are unclear. In vitro functional studies do predict that this variant will impact the protein (Gouas 2005 PMID:16132053, Nishio 2009 PMID:19695459, Nof 2011 PMID:21712262, Du 2013 PMID:24400172). However, these studies may not accurately represent in vivo biological function. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. (less)
|
|
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Likely benign
(Nov 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Long QT syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Blueprint Genetics
Accession: SCV000206985.4
First in ClinVar: Feb 07, 2015 Last updated: Aug 13, 2023 |
Number of individuals with the variant: 28
|
|
|
Likely benign
(Sep 25, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695996.5
First in ClinVar: Oct 09, 2016 Last updated: Nov 04, 2023 |
|
|
|
Likely benign
(Jun 25, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000317782.7
First in ClinVar: Oct 02, 2016 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
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Benign
(Aug 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV000493202.33
First in ClinVar: Oct 09, 2016 Last updated: Oct 20, 2024 |
Comment:
KCNE1: BS1, BS2
Number of individuals with the variant: 13
|
|
|
risk factor
(Aug 01, 2006)
|
no assertion criteria provided
Method: literature only
|
LONG QT SYNDROME 5, ACQUIRED, SUSCEPTIBILITY TO
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000034671.3
First in ClinVar: Apr 04, 2013 Last updated: Aug 15, 2022 |
Comment on evidence:
Long QT Syndrome 5 In a 71-year-old man and an unrelated 81-year-old female with drug-induced torsade de pointes (quinidine and sotolol, respectively), Paulussen et al. … (more)
Long QT Syndrome 5 In a 71-year-old man and an unrelated 81-year-old female with drug-induced torsade de pointes (quinidine and sotolol, respectively), Paulussen et al. (2004) identified heterozygosity for a 253G-A transition in exon 3 of the KCNE1 gene, previously described by Tesson et al. (1996) as a polymorphism, resulting in an asp85-to-asn (D85N) substitution. Both subjects showed QTc prolongation compared to an electrocardiogram recorded prior to drug exposure (613695). The 85N variant was not found in 32 healthy controls. In a female patient who had a QTc of 460 ms and suffered cardiac arrest, Westenskow et al. (2004) identified triallelic digenic mutations: homozygosity for D85N in the KCNE1 gene, and heterozygosity for a missense mutation in the KCNH2 gene (152427.0021). Associations Pending Confirmation In a study of noise-induced hearing loss susceptibility (NIHL; 613035) in 218 Swedish noise-exposed male workers, Van Laer et al. (2006) genotyped 35 SNPs in 10 candidate genes involved in cell coupling and potassium recycling in the inner ear, and identified the 85N variant of KCNE1 in 5 of 104 noise-susceptible individuals and in none of 114 noise-resistant individuals (p = 0.023). Patch-clamp experiments in Chinese hamster ovary (CHO) cells showed a significant difference in current density and midpoint potential between 85N and wildtype channels. The authors suggested that further studies were necessary before KCNE1 D85N could be designated as a causative SNP. (less)
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001553666.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The KCNE1 p.D85N variant was identified in 93 of 4968 proband chromosomes (frequency: 0.0187) from individuals or families with Long QT syndrome (LQTS), however many … (more)
The KCNE1 p.D85N variant was identified in 93 of 4968 proband chromosomes (frequency: 0.0187) from individuals or families with Long QT syndrome (LQTS), however many of these individuals carried variants in other LQTS-related genes (Nishio_2009_PMID:19695459; Lahtinen_2011_PMID:21244686; Kaab_2012_PMID:22100668; Hasegawa_2014, Lane_2018_PMID:29625280). A 10 year old boy with LQTS was found to carry the KCNE1 p.D85N variant along with two other variants: KCNH2 p.N45D and SCN5A p.A1428S, 4282G>T; the proband's unaffected mother and unaffected aunt also carried the KCNE1 p.D85N variant (Yoshikane_2013_PMID:23237912). Another family was reported in which the LQTS-affected proband and daughter carried the KCNE1 p.D85N and KCNH2 p.E58K variants; the proband's unaffected eldest son carried the KCNH2 p.E58K variant and the unaffected youngest son carried the KCNE1 p.D85N variant (Hasegawa_2014). These findings suggest that the p.D85N variant may contribute to or modify disease but likely is not causal. Functional studies demonstrated that the KCNE1 p.D85N variant modified KCNQ1/KCNE1 currents, however this was attenuated when tested in conjunction with another LQTS-associated variant (Hasegawa_2014, Nishio_2009_PMID:19695459). The variant was identified in dbSNP (ID: rs1805128) and ClinVar (classified as benign by Invitae, EGL Genetics and three other laboratories, as likely benign by Laboratory for Molecular Medicine, Ambry Genetics and Illumina, as uncertain significance by Integrated Genetics and CeGaT Praxis fuer Humangenetik Tuebingen, as risk factor by Blueprint Genetics and Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine and as likely pathogenic by Medical Research Institute, Tokyo Medical and Dental University). The variant was identified in control databases in 2637 of 282814 chromosomes (22 homozygous) at a frequency of 0.009324 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Ashkenazi Jewish in 263 of 10368 chromosomes (freq: 0.02537), European (Finnish) in 424 of 25120 chromosomes (freq: 0.01688), European (non-Finnish) in 1580 of 129142 chromosomes (freq: 0.01223), Other in 65 of 7228 chromosomes (freq: 0.008993), East Asian in 111 of 19946 chromosomes (freq: 0.005565), Latino in 97 of 35438 chromosomes (freq: 0.002737), African in 54 of 24956 chromosomes (freq: 0.002164), and South Asian in 43 of 30616 chromosomes (freq: 0.001404). The p.D85 residue is conserved in mammals however four of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. (less)
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|
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not provided
(-)
|
no classification provided
Method: literature only
|
not provided
Affected status: unknown
Allele origin:
germline
|
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust
Accession: SCV000153805.2
First in ClinVar: Jun 03, 2014 Last updated: Oct 09, 2016 |
Comment:
This variant has been reported in the following publications (PMID:9445165;PMID:10807545;PMID:12402336;PMID:14661677;PMID:14760488;PMID:15051636;PMID:15599693;PMID:16132053;PMID:16266404;PMID:16487223;PMID:16887036;PMID:17016049;PMID:17161064;PMID:17210839;PMID:18426444;PMID:19695459;PMID:20823649;PMID:21244686;PMID:21712262;PMID:22100668;PMID:22378279).
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not provided
(-)
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no classification provided
Method: in vitro
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Long QT syndrome 5
Affected status: not applicable
Allele origin:
not applicable
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Roden Lab, Vanderbilt University Medical Center
Accession: SCV005393542.1
First in ClinVar: Nov 10, 2024 Last updated: Nov 10, 2024 |
Comment on evidence:
Functional evidence assertions were derived from functional fitness scores.
Method: Functional assay results from a multiplexed deep mutational scan of KCNE1, measuring cell fitness with Illumina sequencing (a proxy for potassium channel function). Variant outcomes derived from functional score categorization using predefined thresholds and OddsPath assay to determine strength of functional evidence for ACMG/AMP functional assay criteria.
Result:
0.919 - determined to be "normal function"
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Pathogenic
(Aug 01, 2006)
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Flagged submission
flagged submission
Method: literature only
Reason: Outlier claim with insufficient supporting evidence
Source: ClinGen
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LONG QT SYNDROME 2/5, DIGENIC
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000034672.3
First in ClinVar: Apr 04, 2013 Last updated: Aug 15, 2022 |
Comment on evidence:
Long QT Syndrome 5 In a 71-year-old man and an unrelated 81-year-old female with drug-induced torsade de pointes (quinidine and sotolol, respectively), Paulussen et al. … (more)
Long QT Syndrome 5 In a 71-year-old man and an unrelated 81-year-old female with drug-induced torsade de pointes (quinidine and sotolol, respectively), Paulussen et al. (2004) identified heterozygosity for a 253G-A transition in exon 3 of the KCNE1 gene, previously described by Tesson et al. (1996) as a polymorphism, resulting in an asp85-to-asn (D85N) substitution. Both subjects showed QTc prolongation compared to an electrocardiogram recorded prior to drug exposure (613695). The 85N variant was not found in 32 healthy controls. In a female patient who had a QTc of 460 ms and suffered cardiac arrest, Westenskow et al. (2004) identified triallelic digenic mutations: homozygosity for D85N in the KCNE1 gene, and heterozygosity for a missense mutation in the KCNH2 gene (152427.0021). Associations Pending Confirmation In a study of noise-induced hearing loss susceptibility (NIHL; 613035) in 218 Swedish noise-exposed male workers, Van Laer et al. (2006) genotyped 35 SNPs in 10 candidate genes involved in cell coupling and potassium recycling in the inner ear, and identified the 85N variant of KCNE1 in 5 of 104 noise-susceptible individuals and in none of 114 noise-resistant individuals (p = 0.023). Patch-clamp experiments in Chinese hamster ovary (CHO) cells showed a significant difference in current density and midpoint potential between 85N and wildtype channels. The authors suggested that further studies were necessary before KCNE1 D85N could be designated as a causative SNP. (less)
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Likely pathogenic
(-)
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Flagged submission
flagged submission
Method: research
Reason: Outlier claim with insufficient supporting evidence
Source: ClinGen
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Long QT syndrome
Affected status: yes
Allele origin:
germline
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Medical Research Institute, Tokyo Medical and Dental University
Additional submitter:
Division of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo
Accession: SCV000222020.1
First in ClinVar: Aug 07, 2015 Last updated: Aug 07, 2015 |
Method: The mutation was identified with whole-exome sequencing (WES) using Agilent SureSelect V4.
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| Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more | |||||
Comment:
Comment:
This variant is associated with the following publications: (PMID: 19019189, 32429735, 31447099, 31918855, 30384889, 17266934, 29874177, 28798025, 28003625, 29625280, 29540472, 27509294, 14760488, 24400172, 24561134, 19695459, 22999324, 20823649, 25119684, 16823764, 23237912, 23631430, 22995991, 21712262, 16132053, 22378279, 15051636, 22100668, 21244686, 17161064)
Comment:
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, 3.5–22.9) [PMID 22100668]. This variant is considered a risk allele for drug induced long QT.
Comment:
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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
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.
Comment:
KCNE1 c.253G>A (p.Asp85Asn) has been associated with increased risk for long QT syndrome. This variant has been observed in multiple ethnic backgrounds with highest frequencies in individuals of Ashkenazi Jewish ancestry (2.5%, Genome Aggregation Database (gnomAD); rs1805128) and is present in ClinVar (ID: 13479). Several studies have also reported an odds ratio of 4.2-8.9 for developing Long QT syndrome in heterozygous carriers of this variant (OR=8.88 [95% CI 3.26-24.17] Kaab 2011, OR=4.21 [95% CI 1.17-15.16] Gouas 2005). In vitro functional studies provide some evidence that this variant may impact protein function (Nishio 2009). In summary, this variant is a likely risk factor for Long QT syndrome.
Comment:
KCNE1 NM_000219.4 exon 4 p.Asp85Asn (c.253G>A): This variant has been reported in the literature in several individuals with LQTS and is reported to be overrepresented in this patient population compared to control individuals (Westenskow 2004 PMID:15051636, Nishio 2009 PMID:19695459, Kaab 2012 PMID:22100668, Weeke 2014 PMID:24561134, Maltese 2017 PMID:28003625, Lane 2018 PMID:29625280). Several authors in the literature suggest that this variant may act as a risk allele or modifying allele (Gouas 2005 PMID:16132053, Lahtinen 2011 PMID:21244686, Weeke 2014 PMID:24561134, Lane 2018 PMID:29625280). However, this variant is also present in 2.5% (263/10368) of Ashkenazi Jewish alleles in the Genome Aggregation Database, including 5 homozygotes (https://gnomad.broadinstitute.org/variant/21-35821680-C-T), suggesting that it may be a benign polymorphism. This variant is present in ClinVar (Variation ID:13479). Evolutionary conservation and computational predictive tools for this variant are unclear. In vitro functional studies do predict that this variant will impact the protein (Gouas 2005 PMID:16132053, Nishio 2009 PMID:19695459, Nof 2011 PMID:21712262, Du 2013 PMID:24400172). However, these studies may not accurately represent in vivo biological function. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
KCNE1: BS1, BS2
Comment:
The KCNE1 p.D85N variant was identified in 93 of 4968 proband chromosomes (frequency: 0.0187) from individuals or families with Long QT syndrome (LQTS), however many of these individuals carried variants in other LQTS-related genes (Nishio_2009_PMID:19695459; Lahtinen_2011_PMID:21244686; Kaab_2012_PMID:22100668; Hasegawa_2014, Lane_2018_PMID:29625280). A 10 year old boy with LQTS was found to carry the KCNE1 p.D85N variant along with two other variants: KCNH2 p.N45D and SCN5A p.A1428S, 4282G>T; the proband's unaffected mother and unaffected aunt also carried the KCNE1 p.D85N variant (Yoshikane_2013_PMID:23237912). Another family was reported in which the LQTS-affected proband and daughter carried the KCNE1 p.D85N and KCNH2 p.E58K variants; the proband's unaffected eldest son carried the KCNH2 p.E58K variant and the unaffected youngest son carried the KCNE1 p.D85N variant (Hasegawa_2014). These findings suggest that the p.D85N variant may contribute to or modify disease but likely is not causal. Functional studies demonstrated that the KCNE1 p.D85N variant modified KCNQ1/KCNE1 currents, however this was attenuated when tested in conjunction with another LQTS-associated variant (Hasegawa_2014, Nishio_2009_PMID:19695459). The variant was identified in dbSNP (ID: rs1805128) and ClinVar (classified as benign by Invitae, EGL Genetics and three other laboratories, as likely benign by Laboratory for Molecular Medicine, Ambry Genetics and Illumina, as uncertain significance by Integrated Genetics and CeGaT Praxis fuer Humangenetik Tuebingen, as risk factor by Blueprint Genetics and Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine and as likely pathogenic by Medical Research Institute, Tokyo Medical and Dental University). The variant was identified in control databases in 2637 of 282814 chromosomes (22 homozygous) at a frequency of 0.009324 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Ashkenazi Jewish in 263 of 10368 chromosomes (freq: 0.02537), European (Finnish) in 424 of 25120 chromosomes (freq: 0.01688), European (non-Finnish) in 1580 of 129142 chromosomes (freq: 0.01223), Other in 65 of 7228 chromosomes (freq: 0.008993), East Asian in 111 of 19946 chromosomes (freq: 0.005565), Latino in 97 of 35438 chromosomes (freq: 0.002737), African in 54 of 24956 chromosomes (freq: 0.002164), and South Asian in 43 of 30616 chromosomes (freq: 0.001404). The p.D85 residue is conserved in mammals however four of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Comment:
This variant has been reported in the following publications (PMID:9445165;PMID:10807545;PMID:12402336;PMID:14661677;PMID:14760488;PMID:15051636;PMID:15599693;PMID:16132053;PMID:16266404;PMID:16487223;PMID:16887036;PMID:17016049;PMID:17161064;PMID:17210839;PMID:18426444;PMID:19695459;PMID:20823649;PMID:21244686;PMID:21712262;PMID:22100668;PMID:22378279).
Germline Functional Evidence
| Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Effect on ion channel function
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Method citation(s):
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Roden Lab, Vanderbilt University Medical Center
Accession: SCV005393542.1
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Comment:
This variant was studied in a multiplexed assay of variant effect (PMID 38816749). This variant had a mean functional score of 0.919 (0.797-1.041 confidence interval). … (more)
This variant was studied in a multiplexed assay of variant effect (PMID 38816749). This variant had a mean functional score of 0.919 (0.797-1.041 confidence interval). This score is on a scale where the median nonsense variant had a score of 0 and the median synonymous variant had a score of 1. This score was determined to be "normal function". Calibration with control variants resulted in a recommended application of PS3 or BS3 at a maximum of moderate level for this assay. (less)
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Comment:
This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PS3,PS4,PP5,BS1,BP6.
Comment:
This variant is associated with the following publications: (PMID: 19019189, 32429735, 31447099, 31918855, 30384889, 17266934, 29874177, 28798025, 28003625, 29625280, 29540472, 27509294, 14760488, 24400172, 24561134, 19695459, 22999324, 20823649, 25119684, 16823764, 23237912, 23631430, 22995991, 21712262, 16132053, 22378279, 15051636, 22100668, 21244686, 17161064)
Comment:
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, 3.5–22.9) [PMID 22100668]. This variant is considered a risk allele for drug induced long QT.
Comment:
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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
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.
Comment:
KCNE1 c.253G>A (p.Asp85Asn) has been associated with increased risk for long QT syndrome. This variant has been observed in multiple ethnic backgrounds with highest frequencies in individuals of Ashkenazi Jewish ancestry (2.5%, Genome Aggregation Database (gnomAD); rs1805128) and is present in ClinVar (ID: 13479). Several studies have also reported an odds ratio of 4.2-8.9 for developing Long QT syndrome in heterozygous carriers of this variant (OR=8.88 [95% CI 3.26-24.17] Kaab 2011, OR=4.21 [95% CI 1.17-15.16] Gouas 2005). In vitro functional studies provide some evidence that this variant may impact protein function (Nishio 2009). In summary, this variant is a likely risk factor for Long QT syndrome.
Comment:
KCNE1 NM_000219.4 exon 4 p.Asp85Asn (c.253G>A): This variant has been reported in the literature in several individuals with LQTS and is reported to be overrepresented in this patient population compared to control individuals (Westenskow 2004 PMID:15051636, Nishio 2009 PMID:19695459, Kaab 2012 PMID:22100668, Weeke 2014 PMID:24561134, Maltese 2017 PMID:28003625, Lane 2018 PMID:29625280). Several authors in the literature suggest that this variant may act as a risk allele or modifying allele (Gouas 2005 PMID:16132053, Lahtinen 2011 PMID:21244686, Weeke 2014 PMID:24561134, Lane 2018 PMID:29625280). However, this variant is also present in 2.5% (263/10368) of Ashkenazi Jewish alleles in the Genome Aggregation Database, including 5 homozygotes (https://gnomad.broadinstitute.org/variant/21-35821680-C-T), suggesting that it may be a benign polymorphism. This variant is present in ClinVar (Variation ID:13479). Evolutionary conservation and computational predictive tools for this variant are unclear. In vitro functional studies do predict that this variant will impact the protein (Gouas 2005 PMID:16132053, Nishio 2009 PMID:19695459, Nof 2011 PMID:21712262, Du 2013 PMID:24400172). However, these studies may not accurately represent in vivo biological function. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
KCNE1: BS1, BS2
Comment:
The KCNE1 p.D85N variant was identified in 93 of 4968 proband chromosomes (frequency: 0.0187) from individuals or families with Long QT syndrome (LQTS), however many of these individuals carried variants in other LQTS-related genes (Nishio_2009_PMID:19695459; Lahtinen_2011_PMID:21244686; Kaab_2012_PMID:22100668; Hasegawa_2014, Lane_2018_PMID:29625280). A 10 year old boy with LQTS was found to carry the KCNE1 p.D85N variant along with two other variants: KCNH2 p.N45D and SCN5A p.A1428S, 4282G>T; the proband's unaffected mother and unaffected aunt also carried the KCNE1 p.D85N variant (Yoshikane_2013_PMID:23237912). Another family was reported in which the LQTS-affected proband and daughter carried the KCNE1 p.D85N and KCNH2 p.E58K variants; the proband's unaffected eldest son carried the KCNH2 p.E58K variant and the unaffected youngest son carried the KCNE1 p.D85N variant (Hasegawa_2014). These findings suggest that the p.D85N variant may contribute to or modify disease but likely is not causal. Functional studies demonstrated that the KCNE1 p.D85N variant modified KCNQ1/KCNE1 currents, however this was attenuated when tested in conjunction with another LQTS-associated variant (Hasegawa_2014, Nishio_2009_PMID:19695459). The variant was identified in dbSNP (ID: rs1805128) and ClinVar (classified as benign by Invitae, EGL Genetics and three other laboratories, as likely benign by Laboratory for Molecular Medicine, Ambry Genetics and Illumina, as uncertain significance by Integrated Genetics and CeGaT Praxis fuer Humangenetik Tuebingen, as risk factor by Blueprint Genetics and Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine and as likely pathogenic by Medical Research Institute, Tokyo Medical and Dental University). The variant was identified in control databases in 2637 of 282814 chromosomes (22 homozygous) at a frequency of 0.009324 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Ashkenazi Jewish in 263 of 10368 chromosomes (freq: 0.02537), European (Finnish) in 424 of 25120 chromosomes (freq: 0.01688), European (non-Finnish) in 1580 of 129142 chromosomes (freq: 0.01223), Other in 65 of 7228 chromosomes (freq: 0.008993), East Asian in 111 of 19946 chromosomes (freq: 0.005565), Latino in 97 of 35438 chromosomes (freq: 0.002737), African in 54 of 24956 chromosomes (freq: 0.002164), and South Asian in 43 of 30616 chromosomes (freq: 0.001404). The p.D85 residue is conserved in mammals however four of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Comment:
This variant has been reported in the following publications (PMID:9445165;PMID:10807545;PMID:12402336;PMID:14661677;PMID:14760488;PMID:15051636;PMID:15599693;PMID:16132053;PMID:16266404;PMID:16487223;PMID:16887036;PMID:17016049;PMID:17161064;PMID:17210839;PMID:18426444;PMID:19695459;PMID:20823649;PMID:21244686;PMID:21712262;PMID:22100668;PMID:22378279).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome. | Lahrouchi N | Circulation | 2020 | PMID: 32429735 |
| Genetic susceptibility in pharmacodynamic and pharmacokinetic pathways underlying drug-induced arrhythmia and sudden unexplained deaths. | Martinez-Matilla M | Forensic science international. Genetics | 2019 | PMID: 31376648 |
| Cardiac Arrest Associated with Both an Anomalous Left Coronary Artery and KCNE1 Polymorphism. | Kawai H | International heart journal | 2019 | PMID: 31308327 |
| Recent understanding of clinical sequencing and gene-based risk stratification in inherited primary arrhythmia syndrome. | Aiba T | Journal of cardiology | 2019 | PMID: 30910390 |
| Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance. | van Lint FHM | Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation | 2019 | PMID: 30847666 |
| Long QT syndrome type 5-Lite: Defining the clinical phenotype associated with the potentially proarrhythmic p.Asp85Asn-KCNE1 common genetic variant. | Lane CM | Heart rhythm | 2018 | PMID: 29625280 |
| Gene-Targeted Analysis of Clinically Diagnosed Long QT Russian Families. | Maltese PE | International heart journal | 2017 | PMID: 28003625 |
| Patient Outcomes From a Specialized Inherited Arrhythmia Clinic. | Adler A | Circulation. Arrhythmia and electrophysiology | 2016 | PMID: 26743238 |
| Analysis for Genetic Modifiers of Disease Severity in Patients With Long-QT Syndrome Type 2. | Kolder ICRM | Circulation. Cardiovascular genetics | 2015 | PMID: 25737393 |
| Instability of KCNE1-D85N that causes long QT syndrome: stabilization by verapamil. | Sakata S | Pacing and clinical electrophysiology : PACE | 2014 | PMID: 24499369 |
| Modification by KCNE1 variants of the hERG potassium channel response to premature stimulation and to pharmacological inhibition. | Du C | Physiological reports | 2013 | PMID: 24400172 |
| High prevalence of genetic variants previously associated with LQT syndrome in new exome data. | Refsgaard L | European journal of human genetics : EJHG | 2012 | PMID: 22378279 |
| A large candidate gene survey identifies the KCNE1 D85N polymorphism as a possible modulator of drug-induced torsades de pointes. | Kääb S | Circulation. Cardiovascular genetics | 2012 | PMID: 22100668 |
| LQT5 masquerading as LQT2: a dominant negative effect of KCNE1-D85N rare polymorphism on KCNH2 current. | Nof E | Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology | 2011 | PMID: 21712262 |
| KCNE1 D85N polymorphism--a sex-specific modifier in type 1 long QT syndrome? | Lahtinen AM | BMC medical genetics | 2011 | PMID: 21244686 |
| Aborted cardiac arrest in a patient carrying KCNE1 D85N variant during the postpartum period. | Nakajima T | Internal medicine (Tokyo, Japan) | 2010 | PMID: 20823649 |
| D85N, a KCNE1 polymorphism, is a disease-causing gene variant in long QT syndrome. | Nishio Y | Journal of the American College of Cardiology | 2009 | PMID: 19695459 |
| Common variants at ten loci influence QT interval duration in the QTGEN Study. | Newton-Cheh C | Nature genetics | 2009 | PMID: 19305408 |
| Single nucleotide polymorphisms and haplotype of four genes encoding cardiac ion channels in Chinese and their association with arrhythmia. | Zhang Y | Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc | 2008 | PMID: 18426444 |
| Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. | Arnestad M | Circulation | 2007 | PMID: 17210839 |
| The single nucleotide polymorphisms of I(Ks) potassium channel genes and their association with atrial fibrillation in a Chinese population. | Zeng Z | Cardiology | 2007 | PMID: 17016049 |
| Association of torsades de pointes with novel and known single nucleotide polymorphisms in long QT syndrome genes. | Mank-Seymour AR | American heart journal | 2006 | PMID: 17161064 |
| Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome. | Millat G | Clinical genetics | 2006 | PMID: 16922724 |
| Potassium channel gene mutations rarely cause atrial fibrillation. | Ellinor PT | BMC medical genetics | 2006 | PMID: 16887036 |
| The contribution of genes involved in potassium-recycling in the inner ear to noise-induced hearing loss. | Van Laer L | Human mutation | 2006 | PMID: 16823764 |
| Genetic polymorphisms in KCNQ1, HERG, KCNE1 and KCNE2 genes in the Chinese, Malay and Indian populations of Singapore. | Koo SH | British journal of clinical pharmacology | 2006 | PMID: 16487223 |
| Possible association of the human KCNE1 (minK) gene and QT interval in healthy subjects: evidence from association and linkage analyses in Israeli families. | Friedlander Y | Annals of human genetics | 2005 | PMID: 16266404 |
| Association of KCNQ1, KCNE1, KCNH2 and SCN5A polymorphisms with QTc interval length in a healthy population. | Gouas L | European journal of human genetics : EJHG | 2005 | PMID: 16132053 |
| Single nucleotide polymorphism map of five long-QT genes. | Aydin A | Journal of molecular medicine (Berlin, Germany) | 2005 | PMID: 15599693 |
| Compound mutations: a common cause of severe long-QT syndrome. | Westenskow P | Circulation | 2004 | PMID: 15051636 |
| Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. | Paulussen AD | Journal of molecular medicine (Berlin, Germany) | 2004 | PMID: 14760488 |
| Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome. | Ackerman MJ | Mayo Clinic proceedings | 2003 | PMID: 14661677 |
| DHPLC analysis of potassium ion channel genes in congenital long QT syndrome. | Jongbloed R | Human mutation | 2002 | PMID: 12402336 |
| Twenty single nucleotide polymorphisms (SNPs) and their allelic frequencies in four genes that are responsible for familial long QT syndrome in the Japanese population. | Iwasa H | Journal of human genetics | 2000 | PMID: 10807545 |
| Mutation of the gene for IsK associated with both Jervell and Lange-Nielsen and Romano-Ward forms of Long-QT syndrome. | Duggal P | Circulation | 1998 | PMID: 9445165 |
| Exclusion of KCNE1 (IsK) as a candidate gene for Jervell and Lange-Nielsen syndrome. | Tesson F | Journal of molecular and cellular cardiology | 1996 | PMID: 8899564 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=KCNE1 | - | - | - | - |
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Text-mined citations for rs1805128 ...
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at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.