VCV000132670.17 - ClinVar

NM_000219.6(KCNE1):c.23C>T (p.Ala8Val)

Germline

Classification

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.

(9)

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.

Uncertain significance

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000219.6(KCNE1):c.23C>T (p.Ala8Val)

Variation ID: 132670 Accession: VCV000132670.17

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 21q22.12 21: 34449612 (GRCh38) [ NCBI UCSC ] 21: 35821910 (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	Dec 6, 2014	Nov 10, 2024	Jan 16, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000219.6:c.23C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000210.2:p.Ala8Val	missense
NM_001127668.4:c.23C>T	NP_001121140.1:p.Ala8Val	missense
NM_001127669.4:c.23C>T	NP_001121141.1:p.Ala8Val	missense
NM_001127670.4:c.23C>T	NP_001121142.1:p.Ala8Val	missense
NM_001270402.3:c.23C>T	NP_001257331.1:p.Ala8Val	missense
NM_001270403.2:c.23C>T	NP_001257332.1:p.Ala8Val	missense
NM_001270404.3:c.23C>T	NP_001257333.1:p.Ala8Val	missense
NM_001270405.3:c.23C>T	NP_001257334.1:p.Ala8Val	missense
NC_000021.9:g.34449612G>A
NC_000021.8:g.35821910G>A
NG_009091.1:g.66704C>T
LRG_290:g.66704C>T
LRG_290t1:c.23C>T
	P15382:p.Ala8Val

... more HGVS ... less HGVS

Protein change

A8V

Other names

NM_000219.5(KCNE1):c.23C>T(p.Ala8Val)
NM_001127668.3(KCNE1):c.23C>T(p.Ala8Val)
NM_001127669.3(KCNE1):c.23C>T(p.Ala8Val)
NM_001127670.3(KCNE1):c.23C>T(p.Ala8Val)
NM_001270402.2(KCNE1):c.23C>T(p.Ala8Val)
NM_001270403.2(KCNE1):c.23C>T(p.Ala8Val)
NM_001270404.2(KCNE1):c.23C>T(p.Ala8Val)
NM_001270405.2(KCNE1):c.23C>T(p.Ala8Val)

Canonical SPDI

NC_000021.9:34449611:G:A

Functional consequence Help The 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 0.778 (0.703-0.852 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) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008

The Genome Aggregation Database (gnomAD) 0.00011

Links

ClinGen: CA211446 UniProtKB: P15382#VAR_074908 dbSNP: rs199473348 VarSome

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
Gene	OMIM	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.
Congenital long QT syndrome	not provided (1)	no classification provided	-	RCV000119082.2
Long QT syndrome	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Jan 16, 2024	RCV000148516.8
Cardiovascular phenotype	Uncertain significance (1)	criteria provided, single submitter	Mar 17, 2021	RCV000618807.4
not specified	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Jan 13, 2020	RCV000455223.5
Long QT syndrome 5	Uncertain significance (2)	criteria provided, single submitter	May 31, 2018	RCV000677314.2
Jervell and Lange-Nielsen syndrome 2 Long QT syndrome 5	Uncertain significance (1)	criteria provided, single submitter	Nov 15, 2021	RCV002477300.1

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.
Uncertain significance (Aug 09, 2018)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000539419.1 First in ClinVar: Apr 09, 2017 Last updated: Apr 09, 2017	Publications: PubMed (5) PubMed: 19716085‚ 25650408‚ 24400172‚ 18776039‚ 17341399 Comment: The p.Ala8Val variant in KCNE1 has been reported in the heterozygous state in on e individual with paroxysmal atrial fibrillation and sick sinus syndrome and … (more) The p.Ala8Val variant in KCNE1 has been reported in the heterozygous state in on e individual with paroxysmal atrial fibrillation and sick sinus syndrome and one individual with Long QT syndrome (Ohno 2007, Sale 2008, Kapplinger 2009). This variant has been identified in 11/18860 East Asian chromosomes by the Genome Agg regation Database (gnomAD, http://gnomad.broadinstitute.org/) and is reported in ClinVar (Variation ID: 132670). In vitro functional studies provide some eviden ce that the p.Ala8Val variant may impact protein function (Ohno 2007, Sale 2008, Du 2013). However, these types of assays may not accurately represent biologica l function. Alanine (Ala) at position 8 is not conserved in mammals or evolution arily distant species and 4 mammals carry a Valine (Val) at this position, raisi ng the possibility that this change may be tolerated. Additional computational p rediction tools suggest that the p.Ala8Val variant may not impact the protein, t hough this information is not predictive enough to rule out pathogenicity. In su mmary, the clinical significance of the p.Ala8Val variant is uncertain. ACMG/AMP Criteria applied: PS3_Supporting, PS4_Supporting, BP4_Strong. (less) Number of individuals with the variant: 1
Uncertain significance (Nov 15, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Jervell and Lange-Nielsen syndrome 2 Long QT syndrome 5 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002780855.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Uncertain significance (Jan 16, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Long QT syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000549149.6 First in ClinVar: Dec 06, 2014 Last updated: Feb 14, 2024	Publications: PubMed (7) PubMed: 17341399‚ 19716085‚ 31521807‚ 31535183‚ 34403091‚ 18776039‚ 24400172 Comment: This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 8 of the KCNE1 protein (p.Ala8Val). … (more) This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 8 of the KCNE1 protein (p.Ala8Val). This variant is present in population databases (rs199473348, gnomAD 0.06%). This missense change has been observed in individual(s) with long QT syndrome or clinical suspicion of long QT syndrome (PMID: 17341399, 19716085, 31521807, 31535183, 34403091). ClinVar contains an entry for this variant (Variation ID: 132670). 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) performed at Invitae indicates that this missense variant is not expected to disrupt KCNE1 protein function with a negative predictive value of 95%. Experimental studies have shown that this missense change affects KCNE1 function (PMID: 17341399, 18776039, 24400172). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
Uncertain significance (Mar 17, 2021)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cardiovascular phenotype Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000736362.6 First in ClinVar: Apr 14, 2018 Last updated: May 01, 2024	Comment: The c.23C>T (p.A8V) alteration is located in exon 3 (coding exon 1) of the KCNE1 gene. This alteration results from a C to T substitution … (more) The c.23C>T (p.A8V) alteration is located in exon 3 (coding exon 1) of the KCNE1 gene. This alteration results from a C to T substitution at nucleotide position 23, causing the alanine (A) at amino acid position 8 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
Uncertain significance (Jun 01, 2014)	criteria provided, single submitter (Amendola et al. (Genome Res. 2015)) Method: research	Long QT syndrome (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	CSER _CC_NCGL, University of Washington Study: ESP 6500 variant annotation Accession: SCV000190228.2 First in ClinVar: Dec 06, 2014 Last updated: Dec 06, 2014 Comment: Variants classified for the Actionable exomic incidental findings in 6503 participants: challenges of variant classification manuscript	Publications: PubMed (1) PubMed: 25637381 Comment: Low GERP score may suggest that this variant may belong in a lower pathogenicity class
Uncertain significance (Jan 13, 2020)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV001337808.1 First in ClinVar: Jun 18, 2020 Last updated: Jun 18, 2020	Publications: PubMed (17) PubMed: 19716085‚ 19695459‚ 17341399‚ 25650408‚ 19862833‚ 26715165‚ 24400172‚ 26410412‚ 28767663‚ 31535183‚ 26926294‚ 30461122‚ 20541041‚ 28988457‚ 31521807‚ 18776039‚ 30123799 Comment: Variant summary: KCNE1 c.23C>T (p.Ala8Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign … (more) Variant summary: KCNE1 c.23C>T (p.Ala8Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 251512 control chromosomes. The observed variant frequency is approximately 10.7- fold the estimated maximal expected allele frequency for a pathogenic variant in KCNE1 causing Arrhythmia phenotype (1e-05), suggesting that the variant is benign. However, c.23C>T has been reported in the literature in multiple individuals affected with arrhythmia (e.g. Ohno_2007, Sale_2008, Kapplinger_2009, Fedida_2017, Bennett_2019, Li_2019), including three individuals from one family in which the variant segregated with a Long QT Syndrome (LQTS) phenotype (Li_2019). These data indicate that the variant may be associated with disease. At least three publications report experimental evidence evaluating the electrophysiological effects of the variant on potassium channels and suggest that the variant may alter channel kinetics, however the biological consequences fo these findings are not clear (e.g. Ohno_2007, Sale, 2008, Du_2013). Four other ClinVar submitters (evaluation after 2014) have cited the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
Uncertain significance (May 31, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: curation	Long QT syndrome 5 Affected status: unknown Allele origin: unknown	SIB Swiss Institute of Bioinformatics Accession: SCV000803462.1 First in ClinVar: Aug 20, 2018 Last updated: Aug 20, 2018	Publications: PubMed (1) PubMed: 18776039 Comment: This variant is interpreted as a Uncertain Significance - Conflicting Evidence, for Long QT syndrome 5, in Autosomal Dominant manner. The following ACMG Tag(s) were … (more) This variant is interpreted as a Uncertain Significance - Conflicting Evidence, for Long QT syndrome 5, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder. PS3-Moderate => PS3 downgraded in strength to Moderate (PMID:18776039). (less)
not provided (-)	no classification provided Method: literature only	Congenital long QT syndrome Affected status: unknown Allele origin: germline	Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust Accession: SCV000153801.2 First in ClinVar: Jun 03, 2014 Last updated: Oct 09, 2016	Publications: PubMed (3) PubMed: 22581653‚ 17341399‚ 19716085 Comment: This variant has been reported as associated with Long QT syndrome in the following publications (PMID:17341399;PMID:19716085). This is a literature report, and does not necessarily … (more) This variant has been reported as associated with Long QT syndrome in the following publications (PMID:17341399;PMID:19716085). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. (less)
not provided (-)	no classification provided Method: in vitro	Long QT syndrome 5 Affected status: not applicable Allele origin: not applicable	Roden Lab, Vanderbilt University Medical Center Accession: SCV005393484.1 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: 0.778 - determined to be "normal function"

Comment:

The p.Ala8Val variant in KCNE1 has been reported in the heterozygous state in on e individual with paroxysmal atrial fibrillation and sick sinus syndrome and one individual with Long QT syndrome (Ohno 2007, Sale 2008, Kapplinger 2009). This variant has been identified in 11/18860 East Asian chromosomes by the Genome Agg regation Database (gnomAD, http://gnomad.broadinstitute.org/) and is reported in ClinVar (Variation ID: 132670). In vitro functional studies provide some eviden ce that the p.Ala8Val variant may impact protein function (Ohno 2007, Sale 2008, Du 2013). However, these types of assays may not accurately represent biologica l function. Alanine (Ala) at position 8 is not conserved in mammals or evolution arily distant species and 4 mammals carry a Valine (Val) at this position, raisi ng the possibility that this change may be tolerated. Additional computational p rediction tools suggest that the p.Ala8Val variant may not impact the protein, t hough this information is not predictive enough to rule out pathogenicity. In su mmary, the clinical significance of the p.Ala8Val variant is uncertain. ACMG/AMP Criteria applied: PS3_Supporting, PS4_Supporting, BP4_Strong.

Comment:

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 8 of the KCNE1 protein (p.Ala8Val). This variant is present in population databases (rs199473348, gnomAD 0.06%). This missense change has been observed in individual(s) with long QT syndrome or clinical suspicion of long QT syndrome (PMID: 17341399, 19716085, 31521807, 31535183, 34403091). ClinVar contains an entry for this variant (Variation ID: 132670). 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) performed at Invitae indicates that this missense variant is not expected to disrupt KCNE1 protein function with a negative predictive value of 95%. Experimental studies have shown that this missense change affects KCNE1 function (PMID: 17341399, 18776039, 24400172). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Comment:

The c.23C>T (p.A8V) alteration is located in exon 3 (coding exon 1) of the KCNE1 gene. This alteration results from a C to T substitution at nucleotide position 23, causing the alanine (A) at amino acid position 8 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Comment:

Variant summary: KCNE1 c.23C>T (p.Ala8Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 251512 control chromosomes. The observed variant frequency is approximately 10.7- fold the estimated maximal expected allele frequency for a pathogenic variant in KCNE1 causing Arrhythmia phenotype (1e-05), suggesting that the variant is benign. However, c.23C>T has been reported in the literature in multiple individuals affected with arrhythmia (e.g. Ohno_2007, Sale_2008, Kapplinger_2009, Fedida_2017, Bennett_2019, Li_2019), including three individuals from one family in which the variant segregated with a Long QT Syndrome (LQTS) phenotype (Li_2019). These data indicate that the variant may be associated with disease. At least three publications report experimental evidence evaluating the electrophysiological effects of the variant on potassium channels and suggest that the variant may alter channel kinetics, however the biological consequences fo these findings are not clear (e.g. Ohno_2007, Sale, 2008, Du_2013). Four other ClinVar submitters (evaluation after 2014) have cited the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

Comment:

This variant is interpreted as a Uncertain Significance - Conflicting Evidence, for Long QT syndrome 5, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder. PS3-Moderate => PS3 downgraded in strength to Moderate (PMID:18776039).

Comment:

This variant has been reported as associated with Long QT syndrome in the following publications (PMID:17341399;PMID:19716085). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

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.
Effect on ion channel function (FENICS-0001)	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. Method citation(s): PubMed(1)	0.778 - determined to be "normal function"	Roden Lab, Vanderbilt University Medical Center Accession: SCV005393484.1	Comment: This variant was studied in a multiplexed assay of variant effect (PMID 38816749). This variant had a mean functional score of 0.778 (0.703-0.852 confidence interval). … (more) This variant was studied in a multiplexed assay of variant effect (PMID 38816749). This variant had a mean functional score of 0.778 (0.703-0.852 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)

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Genetic Susceptibility Study of Chinese Sudden Sensorineural Hearing Loss Patients with Vertigo.	Gao Y	Current medical science	2021	PMID: 34403091
Genetic arrhythmias complicating patients with dilated cardiomyopathy.	Li Z	Heart rhythm	2020	PMID: 31521807
Reclassification of Variants of Uncertain Significance in Children with Inherited Arrhythmia Syndromes is Predicted by Clinical Factors.	Bennett JS	Pediatric cardiology	2019	PMID: 31535183
Mutational and phenotypic spectra of KCNE1 deficiency in Jervell and Lange-Nielsen Syndrome and Romano-Ward Syndrome.	Faridi R	Human mutation	2019	PMID: 30461122
Long QT Syndrome and Sinus Bradycardia-A Mini Review.	Wilders R	Frontiers in cardiovascular medicine	2018	PMID: 30123799
Re-evaluating pathogenicity of variants associated with the long QT syndrome.	Kaltman JR	Journal of cardiovascular electrophysiology	2018	PMID: 28988457
Contribution of exome sequencing for genetic diagnostic in arrhythmogenic right ventricular cardiomyopathy/dysplasia.	Fedida J	PloS one	2017	PMID: 28767663
Drug-induced Inhibition and Trafficking Disruption of ion Channels: Pathogenesis of QT Abnormalities and Drug-induced Fatal Arrhythmias.	Cubeddu LX	Current cardiology reviews	2016	PMID: 26926294
The genetics underlying acquired long QT syndrome: impact for genetic screening.	Itoh H	European heart journal	2016	PMID: 26715165
KCNE1 and KCNE3: The yin and yang of voltage-gated K(+) channel regulation.	Abbott GW	Gene	2016	PMID: 26410412
Testing the burden of rare variation in arrhythmia-susceptibility genes provides new insights into molecular diagnosis for Brugada syndrome.	Le Scouarnec S	Human molecular genetics	2015	PMID: 25650408
Modification by KCNE1 variants of the hERG potassium channel response to premature stimulation and to pharmacological inhibition.	Du C	Physiological reports	2013	PMID: 24400172
Long QT syndrome with compound mutations is associated with a more severe phenotype: a Japanese multicenter study.	Itoh H	Heart rhythm	2010	PMID: 20541041
The genetic basis of long QT and short QT syndromes: a mutation update.	Hedley PL	Human mutation	2009	PMID: 19862833
Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.	Kapplinger JD	Heart rhythm	2009	PMID: 19716085
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
Physiological properties of hERG 1a/1b heteromeric currents and a hERG 1b-specific mutation associated with Long-QT syndrome.	Sale H	Circulation research	2008	PMID: 18776039
N- and C-terminal KCNE1 mutations cause distinct phenotypes of long QT syndrome.	Ohno S	Heart rhythm	2007	PMID: 17341399
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Text-mined citations for rs199473348 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 10, 2024

ClinVar Genomic variation as it relates to human health

NM_000219.6(KCNE1):c.23C>T (p.Ala8Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs199473348 ...