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NM_005477.3(HCN4):c.1444G>A (p.Gly482Arg)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
3 (Most recent: Aug 17, 2021)
Last evaluated:
Oct 2, 2020
Accession:
VCV000197253.6
Variation ID:
197253
Description:
single nucleotide variant
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NM_005477.3(HCN4):c.1444G>A (p.Gly482Arg)

Allele ID
194414
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
15q24.1
Genomic location
15: 73329719 (GRCh38) GRCh38 UCSC
15: 73622060 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000015.10:g.73329719C>T
NC_000015.9:g.73622060C>T
NG_009063.1:g.44546G>A
NM_005477.3:c.1444G>A MANE Select NP_005468.1:p.Gly482Arg missense
Protein change
G482R
Other names
-
Canonical SPDI
NC_000015.10:73329718:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA202778
dbSNP: rs794727637
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Oct 2, 2020 RCV000178241.4
Pathogenic 1 criteria provided, single submitter Jul 21, 2020 RCV000647252.4
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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
Likely pathogenic
(Jun 09, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000230285.5
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (2)
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(Jul 21, 2020)
criteria provided, single submitter
Method: clinical testing
Brugada syndrome 8
Allele origin: germline
Invitae
Accession: SCV000769041.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces glycine with arginine at codon 482 of the HCN4 protein (p.Gly482Arg). The glycine residue is highly conserved and there is a … (more)
Pathogenic
(Oct 02, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001791508.1
Submitted: (Aug 17, 2021)
Evidence details
Comment:
Reported G482R to segregate with bradycardia and left ventricular non-compaction cardiomyopathy (LVNC) in six members of one Dutch family and in three French sisters (Milano … (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
Dilation of the Aorta Ascendens Forms Part of the Clinical Spectrum of HCN4 Mutations. Vermeer AMC Journal of the American College of Cardiology 2016 PMID: 27173043
HCN4 mutation as a molecular explanation on patients with bradycardia and non-compaction cardiomyopathy. Millat G European journal of medical genetics 2015 PMID: 26206080
The symptom complex of familial sinus node dysfunction and myocardial noncompaction is associated with mutations in the HCN4 channel. Schweizer PA Journal of the American College of Cardiology 2014 PMID: 25145518
HCN4 mutations in multiple families with bradycardia and left ventricular noncompaction cardiomyopathy. Milano A Journal of the American College of Cardiology 2014 PMID: 25145517
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=HCN4 - - - -

Text-mined citations for rs794727637...

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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 Sep 24, 2021