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NM_005477.3(HCN4):c.3414del (p.Arg1140fs)

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Interpretation:
Uncertain significance​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
2 (Most recent: Jan 7, 2021)
Last evaluated:
Dec 19, 2019
Accession:
VCV000518849.5
Variation ID:
518849
Description:
1bp deletion
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NM_005477.3(HCN4):c.3414del (p.Arg1140fs)

Allele ID
510666
Variant type
Deletion
Variant length
1 bp
Cytogenetic location
15q24.1
Genomic location
15: 73322679 (GRCh38) GRCh38 UCSC
15: 73615020 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000015.10:g.73322679del
NC_000015.9:g.73615020del
NG_009063.1:g.51586del
... more HGVS
Protein change
R1140fs
Other names
-
Canonical SPDI
NC_000015.10:73322678:A:
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
The Genome Aggregation Database (gnomAD), exomes 0.00001
Links
ClinGen: CA7648826
dbSNP: rs746402732
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Feb 15, 2017 RCV000621990.1
Uncertain significance 1 criteria provided, single submitter Dec 19, 2019 RCV001059075.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
HCN4 - - GRCh38
GRCh37
782 816

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Feb 15, 2017)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000736407.3
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (3)
Comment:
<p style="text-align:justify">The c.3414delT variant, located in coding exon 8 of the HCN4 gene, results from a deletion of one nucleotide at nucleotide position 3414, causing … (more)
Uncertain significance
(Dec 19, 2019)
criteria provided, single submitter
Method: clinical testing
Brugada syndrome 8
Allele origin: germline
Invitae
Accession: SCV001223681.2
Submitted: (Jan 07, 2021)
Evidence details
Comment:
This sequence change results in a premature translational stop signal in the HCN4 gene (p.Arg1140Glyfs*41). While this is not anticipated to result in nonsense mediated … (more)

Functional evidence

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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.

Citations for this variant

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Title Author Journal Year Link
cAMP sensitivity of HCN pacemaker channels determines basal heart rate but is not critical for autonomic rate control. Schweizer PA Circulation. Arrhythmia and electrophysiology 2010 PMID: 20693575
Role of HCN4 channel in preventing ventricular arrhythmia. Ueda K Journal of human genetics 2009 PMID: 19165230
Pacemaker channel dysfunction in a patient with sinus node disease. Schulze-Bahr E The Journal of clinical investigation 2003 PMID: 12750403

Text-mined citations for rs746402732...

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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 Oct 08, 2021