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NM_005477.3(HCN4):c.1132C>T (p.Arg378Cys)

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Interpretation:
Uncertain significance​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
5 (Most recent: Sep 30, 2021)
Last evaluated:
Nov 19, 2019
Accession:
VCV000190779.8
Variation ID:
190779
Description:
single nucleotide variant
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NM_005477.3(HCN4):c.1132C>T (p.Arg378Cys)

Allele ID
188640
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
15q24.1
Genomic location
15: 73343462 (GRCh38) GRCh38 UCSC
15: 73635803 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000015.10:g.73343462G>A
NC_000015.9:g.73635803G>A
NG_009063.1:g.30803C>T
NM_005477.3:c.1132C>T MANE Select NP_005468.1:p.Arg378Cys missense
Protein change
R378C
Other names
p.R378C:CGC>TGC
Canonical SPDI
NC_000015.10:73343461:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00002
Exome Aggregation Consortium (ExAC) 0.00002
Links
ClinGen: CA301958
dbSNP: rs758468167
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 3 criteria provided, single submitter May 1, 2014 RCV000170938.5
Uncertain significance 1 criteria provided, single submitter May 4, 2017 RCV000619663.1
Uncertain significance 1 criteria provided, single submitter Nov 19, 2019 RCV001051690.2
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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
781 815

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(May 01, 2014)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000223498.11
Submitted: (Jan 29, 2019)
Evidence details
Comment:
p.Arg378Cys (CGC>TGC): c.1132 C>T in exon 2 of the HCN4 gene (NM_005477.2). To our knowledge, the R378C variant has not been published as a mutation … (more)
Uncertain significance
(May 04, 2017)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000737997.3
Submitted: (Nov 30, 2020)
Evidence details
Comment:
The p.R378C variant (also known as c.1132C>T), located in coding exon 2 of the HCN4 gene, results from a C to T substitution at nucleotide … (more)
Uncertain significance
(Nov 19, 2019)
criteria provided, single submitter
Method: clinical testing
Brugada syndrome 8
Allele origin: germline
Invitae
Accession: SCV001215858.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change replaces arginine with cysteine at codon 378 of the HCN4 protein (p.Arg378Cys). The arginine residue is highly conserved and there is a … (more)
Uncertain significance
(-)
no assertion criteria provided
Method: clinical testing
not provided
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: SCV001925478.1
Submitted: (Sep 23, 2021)
Evidence details
Uncertain significance
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Human Genetics - Radboudumc,Radboudumc
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001957556.1
Submitted: (Sep 30, 2021)
Evidence details

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
In Vitro Analyses of Novel HCN4 Gene Mutations. Möller M Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2018 PMID: 30196304

Text-mined citations for rs758468167...

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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