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NM_005477.3(HCN4):c.1123C>T (p.Arg375Cys)

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Interpretation:
Uncertain significance​

Review status:
criteria provided, single submitter
Submissions:
1 (Most recent: Jan 7, 2021)
Last evaluated:
Nov 15, 2019
Accession:
VCV000571947.3
Variation ID:
571947
Description:
single nucleotide variant
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NM_005477.3(HCN4):c.1123C>T (p.Arg375Cys)

Allele ID
573524
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
15q24.1
Genomic location
15: 73343471 (GRCh38) GRCh38 UCSC
15: 73635812 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000015.10:g.73343471G>A
NC_000015.9:g.73635812G>A
NG_009063.1:g.30794C>T
NM_005477.3:c.1123C>T MANE Select NP_005468.1:p.Arg375Cys missense
Protein change
R375C
Other names
-
Canonical SPDI
NC_000015.10:73343470:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00001
Links
dbSNP: rs755356387
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 Nov 15, 2019 RCV000693215.2
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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
(Nov 15, 2019)
criteria provided, single submitter
Method: clinical testing
Brugada syndrome 8
Allele origin: germline
Invitae
Accession: SCV000821075.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change replaces arginine with cysteine at codon 375 of the HCN4 protein (p.Arg375Cys). The arginine residue is highly conserved and there is a … (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
Functional reclassification of variants of uncertain significance in the HCN4 gene identified in sudden unexpected death. Dong J Pacing and clinical electrophysiology : PACE 2019 PMID: 30578647
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
A fast and cost-effective molecular diagnostic tool for genetic diseases involved in sudden cardiac death. Chanavat V Clinica chimica acta; international journal of clinical chemistry 2016 PMID: 26688388

Text-mined citations for rs755356387...

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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