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NM_005477.3(HCN4):c.2995C>T (p.Arg999Trp)

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Interpretation:
Uncertain significance​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
2 (Most recent: Sep 1, 2021)
Last evaluated:
Aug 26, 2020
Accession:
VCV000575202.7
Variation ID:
575202
Description:
single nucleotide variant
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NM_005477.3(HCN4):c.2995C>T (p.Arg999Trp)

Allele ID
573511
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
15q24.1
Genomic location
15: 73323098 (GRCh38) GRCh38 UCSC
15: 73615439 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000015.10:g.73323098G>A
NC_000015.9:g.73615439G>A
NG_009063.1:g.51167C>T
NM_005477.3:c.2995C>T MANE Select NP_005468.1:p.Arg999Trp missense
Protein change
R999W
Other names
-
Canonical SPDI
NC_000015.10:73323097:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (A)

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00007
1000 Genomes Project 0.00020
Links
dbSNP: rs538668505
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 Aug 26, 2020 RCV000697356.4
Uncertain significance 1 criteria provided, single submitter Sep 20, 2019 RCV001585639.3
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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
(Aug 26, 2020)
criteria provided, single submitter
Method: clinical testing
Brugada syndrome 8
Allele origin: germline
Invitae
Accession: SCV000825959.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change replaces arginine with tryptophan at codon 999 of the HCN4 protein (p.Arg999Trp). The arginine residue is highly conserved and there is a … (more)
Uncertain significance
(Sep 20, 2019)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001819402.1
Submitted: (Sep 01, 2021)
Evidence details
Comment:
Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., … (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
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

Text-mined citations for rs538668505...

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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