VCV000220202.32 - ClinVar

NM_000238.4(KCNH2):c.1809C>T (p.Gly603=)

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.

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_000238.4(KCNH2):c.1809C>T (p.Gly603=)

Variation ID: 220202 Accession: VCV000220202.32

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q36.1 7: 150951584 (GRCh38) [ NCBI UCSC ] 7: 150648672 (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, 2016	Sep 29, 2024	Feb 5, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000238.4:c.1809C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000229.1:p.Gly603=	synonymous
NM_000238.2:c.1809C>T
NM_001204798.2:c.789C>T	NP_001191727.1:p.Gly263=	synonymous
NM_001406753.1:c.1521C>T	NP_001393682.1:p.Gly507=	synonymous
NM_001406755.1:c.1632C>T	NP_001393684.1:p.Gly544=	synonymous
NM_001406756.1:c.1521C>T	NP_001393685.1:p.Gly507=	synonymous
NM_001406757.1:c.1509C>T	NP_001393686.1:p.Gly503=	synonymous
NM_172056.3:c.1809C>T	NP_742053.1:p.Gly603=	synonymous
NM_172057.3:c.789C>T	NP_742054.1:p.Gly263=	synonymous
NR_176254.1:n.2217C>T		non-coding transcript variant
NR_176255.1:n.1090C>T		non-coding transcript variant
NC_000007.14:g.150951584G>A
NC_000007.13:g.150648672G>A
NG_008916.1:g.31343C>T
LRG_288:g.31343C>T
LRG_288t1:c.1809C>T	LRG_288p1:p.Gly603=
LRG_288t2:c.1809C>T	LRG_288p2:p.Gly603=
LRG_288t3:c.789C>T	LRG_288p3:p.Gly263=

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000007.14:150951583:G:A

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.

0.01558 (A)

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

The Genome Aggregation Database (gnomAD), exomes 0.00331

Exome Aggregation Consortium (ExAC) 0.00410

Trans-Omics for Precision Medicine (TOPMed) 0.01397

The Genome Aggregation Database (gnomAD) 0.01398

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01538

1000 Genomes Project 0.01558

1000 Genomes Project 30x 0.01671

Links

ClinGen: CA029511 dbSNP: rs41314375 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.
KCNH2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	3223	3309

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.
Long QT syndrome	Benign (2)	criteria provided, multiple submitters, no conflicts	Feb 5, 2024	RCV000205663.25
Cardiovascular phenotype	Benign (1)	criteria provided, single submitter	Jun 26, 2015	RCV000620782.11
not provided	Benign (4)	criteria provided, multiple submitters, no conflicts	Oct 11, 2023	RCV000712074.20
Long QT syndrome 2	Benign (1)	criteria provided, single submitter	Jan 13, 2018	RCV001095279.12
Cardiac arrhythmia	Benign (1)	criteria provided, single submitter	Mar 16, 2018	RCV001842957.10

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 (Feb 06, 2018)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV000842488.1 First in ClinVar: Oct 20, 2018 Last updated: Oct 20, 2018
Benign (Mar 16, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Arrhythmia Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000903352.1 First in ClinVar: May 20, 2019 Last updated: May 20, 2019
Benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Long QT syndrome 2 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000467518.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (Mar 03, 2015)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001942800.2 First in ClinVar: Sep 29, 2021 Last updated: Mar 04, 2023
Benign (Oct 11, 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: SCV001159743.3 First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024
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: SCV000260573.11 First in ClinVar: Feb 02, 2016 Last updated: Feb 28, 2024
Benign (Feb 05, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Long QT syndrome (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	All of Us Research Program, National Institutes of Health Accession: SCV004843948.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 Comment: This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more) This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)	Number of individuals with the variant: 740
Benign (Jun 26, 2015)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cardiovascular phenotype Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000735227.5 First in ClinVar: Apr 14, 2018 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 dominant inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005272857.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs41314375 ...

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_000238.4(KCNH2):c.1809C>T (p.Gly603=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs41314375 ...