VCV000132651.46 - ClinVar

NM_000219.6(KCNE1):c.112A>G (p.Ser38Gly)

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.

(20)

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.

Benign

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.112A>G (p.Ser38Gly)

Variation ID: 132651 Accession: VCV000132651.46

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 21q22.12 21: 34449523 (GRCh38) [ NCBI UCSC ] 21: 35821821 (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	Sep 14, 2015	Sep 29, 2024	Feb 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000219.6:c.112A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000210.2:p.Ser38Gly	missense
NM_001127668.4:c.112A>G	NP_001121140.1:p.Ser38Gly	missense
NM_001127669.4:c.112A>G	NP_001121141.1:p.Ser38Gly	missense
NM_001127670.4:c.112A>G	NP_001121142.1:p.Ser38Gly	missense
NM_001270402.3:c.112A>G	NP_001257331.1:p.Ser38Gly	missense
NM_001270403.2:c.112A>G	NP_001257332.1:p.Ser38Gly	missense
NM_001270404.3:c.112A>G	NP_001257333.1:p.Ser38Gly	missense
NM_001270405.3:c.112A>G	NP_001257334.1:p.Ser38Gly	missense
NC_000021.9:g.34449523T>C
NC_000021.8:g.35821821T>C
NG_009091.1:g.66793A>G
LRG_290:g.66793A>G
LRG_290t1:c.112A>G
	P15382:p.Ser38Gly

... more HGVS ... less HGVS

Protein change

S38G

Other names

p.S38G:AGT>GGT

Canonical SPDI

NC_000021.9:34449522:T:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

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.

0.32608 (T)

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

The Genome Aggregation Database (gnomAD) 0.00019

The Genome Aggregation Database (gnomAD), exomes 0.64284

Exome Aggregation Consortium (ExAC) 0.64771

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.66193

1000 Genomes Project 0.67392

Links

ClinGen: CA131330 UniProtKB: P15382#VAR_001558 dbSNP: rs1805127 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.
not specified	Benign (9)	criteria provided, multiple submitters, no conflicts	Oct 28, 2019	RCV000035351.32
Cardiovascular phenotype	Benign (1)	criteria provided, single submitter	Mar 9, 2015	RCV000241651.11
Noise induced hearing loss	Benign (1)	criteria provided, single submitter	Jun 24, 2013	RCV000171811.11
Congenital long QT syndrome	Benign (1)	criteria provided, single submitter	Jun 14, 2016	RCV000352011.13
not provided	Benign (3)	criteria provided, multiple submitters, no conflicts	Nov 29, 2023	RCV000119063.26
Long QT syndrome 5	Benign (2)	criteria provided, multiple submitters, no conflicts	Aug 19, 2021	RCV001094634.14
Jervell and Lange-Nielsen syndrome 2	Benign (2)	criteria provided, multiple submitters, no conflicts	Aug 19, 2021	RCV000312558.15
Long QT syndrome	Benign (1)	criteria provided, single submitter	Feb 1, 2024	RCV000398637.16

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.
Benign (Jun 24, 2013)	criteria provided, single submitter (Ng et al. (Circ Cardiovasc Genet. 2013)) Method: research	noise-induced hearing loss, susceptibility to Affected status: unknown Allele origin: unknown	Biesecker Lab/Clinical Genomics Section, National Institutes of Health Study: ClinSeq Accession: SCV000050823.2 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. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for … (more) The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for details. (less) Medical sequencing	Number of individuals with the variant: 752
Benign (Apr 08, 2013)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000169911.9 First in ClinVar: Jun 23, 2014 Last updated: Oct 02, 2016	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Benign (Jun 11, 2014)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000228823.5 First in ClinVar: Jun 28, 2015 Last updated: Oct 02, 2016	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=KCNE1 Number of individuals with the variant: 1 Sex: mixed
Benign (Oct 28, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: yes Allele origin: germline	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute Accession: SCV001433064.1 First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000303048.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Romano-Ward Syndrome Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000435788.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Benign (May 07, 2012)	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: SCV000058999.5 First in ClinVar: May 03, 2013 Last updated: Oct 02, 2016	Comment: Ser38Gly in Exon 03 of KCNE1: This variant is not expected to have clinical sign ificance because it has been identified in 37.2% (2612/7020) of … (more) Ser38Gly in Exon 03 of KCNE1: This variant is not expected to have clinical sign ificance because it has been identified in 37.2% (2612/7020) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs1805127). (less) Number of individuals with the variant: 1485
Benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Long QT syndrome 5 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000435789.3 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
Benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Jervell and Lange-Nielsen syndrome 2 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000435790.3 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
Benign (Feb 01, 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: SCV001000355.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024
Benign (Nov 29, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV001156891.8 First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024
Benign (Mar 09, 2015)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cardiovascular phenotype Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000317658.7 First in ClinVar: Oct 02, 2016 Last updated: May 01, 2024	Comment: This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more) This alteration is classified as 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)
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005310015.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (Aug 19, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Long QT syndrome 5 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001980873.1 First in ClinVar: Oct 25, 2021 Last updated: Oct 25, 2021
Benign (Aug 19, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Jervell and Lange-Nielsen syndrome 2 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001980872.1 First in ClinVar: Oct 25, 2021 Last updated: Oct 25, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001744919.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001917914.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001952830.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001965470.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
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: SCV000153782.2 First in ClinVar: Jun 03, 2014 Last updated: May 29, 2016	Publications: PubMed (12) PubMed: 22581653‚ 18426444‚ 17597962‚ 12402336‚ 14760488‚ 16487223‚ 17210839‚ 9445165‚ 7828904‚ 15599693‚ 17161064‚ 14661677 Comment: This variant has been reported in the following publications (PMID:18426444;PMID:17597962;PMID:12402336;PMID:14760488;PMID:16487223;PMID:17210839;PMID:9445165;PMID:7828904;PMID:15599693;PMID:17161064;PMID:14661677).
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Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

Ser38Gly in Exon 03 of KCNE1: This variant is not expected to have clinical sign ificance because it has been identified in 37.2% (2612/7020) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs1805127).

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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.

Comment:

This alteration is classified as 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.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
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
Mutation screening in KCNQ1, HERG, KCNE1, KCNE2 and SCN5A genes in a long QT syndrome family.	Koo SH	Annals of the Academy of Medicine, Singapore	2007	PMID: 17597962
Prevalence of long-QT syndrome gene variants in sudden infant death syndrome.	Arnestad M	Circulation	2007	PMID: 17210839
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
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
Single nucleotide polymorphism map of five long-QT genes.	Aydin A	Journal of molecular medicine (Berlin, Germany)	2005	PMID: 15599693
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
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
Polymorphism of the gene encoding a human minimal potassium ion channel (minK).	Lai LP	Gene	1994	PMID: 7828904
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=KCNE1	-	-	-	-
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Text-mined citations for rs1805127 ...

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.112A>G (p.Ser38Gly)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1805127 ...