Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_005477.3(HCN4):c.2197G>A (p.Val733Ile)

Help
Interpretation:
Uncertain significance​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
4 (Most recent: Sep 2, 2021)
Last evaluated:
Sep 29, 2020
Accession:
VCV000222648.4
Variation ID:
222648
Description:
single nucleotide variant
Help

NM_005477.3(HCN4):c.2197G>A (p.Val733Ile)

Allele ID
224510
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
15q24.1
Genomic location
15: 73323896 (GRCh38) GRCh38 UCSC
15: 73616237 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000015.10:g.73323896C>T
NC_000015.9:g.73616237C>T
NG_009063.1:g.50369G>A
NM_005477.3:c.2197G>A MANE Select NP_005468.1:p.Val733Ile missense
Protein change
V733I
Other names
-
Canonical SPDI
NC_000015.10:73323895:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (T)

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00006
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
1000 Genomes Project 0.00020
The Genome Aggregation Database (gnomAD), exomes 0.00008
Trans-Omics for Precision Medicine (TOPMed) 0.00008
Links
ClinGen: CA068221
dbSNP: rs376631391
VarSome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Sep 29, 2020 RCV000379734.3
Uncertain significance 1 criteria provided, single submitter Nov 16, 2015 RCV000208061.1
Uncertain significance 1 criteria provided, single submitter Oct 25, 2018 RCV000697233.2
Help
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

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Nov 16, 2015)
criteria provided, single submitter
Method: clinical testing
Cardiac arrest
Allele origin: germline
Blueprint Genetics
Accession: SCV000263948.2
Submitted: (Jan 15, 2016)
Evidence details
Uncertain significance
(Jul 20, 2015)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000332956.4
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Uncertain significance
(Oct 25, 2018)
criteria provided, single submitter
Method: clinical testing
Brugada syndrome 8
Allele origin: germline
Invitae
Accession: SCV000825830.2
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change replaces valine with isoleucine at codon 733 of the HCN4 protein (p.Val733Ile). The valine residue is highly conserved and there is a … (more)
Uncertain significance
(Sep 29, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001826240.1
Submitted: (Sep 02, 2021)
Evidence details
Comment:
Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function

Functional evidence

Help
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

Help
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
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=HCN4 - - - -

Text-mined citations for rs376631391...

Help
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