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NM_005477.3(HCN4):c.2730C>A (p.Phe910Leu)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(2);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
4 (Most recent: Jan 7, 2021)
Last evaluated:
Dec 4, 2020
Accession:
VCV000264440.8
Variation ID:
264440
Description:
single nucleotide variant
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NM_005477.3(HCN4):c.2730C>A (p.Phe910Leu)

Allele ID
258952
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
15q24.1
Genomic location
15: 73323363 (GRCh38) GRCh38 UCSC
15: 73615704 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000015.10:g.73323363G>T
NC_000015.9:g.73615704G>T
NG_009063.1:g.50902C>A
NM_005477.3:c.2730C>A MANE Select NP_005468.1:p.Phe910Leu missense
Protein change
F910L
Other names
-
Canonical SPDI
NC_000015.10:73323362:G:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Exome Aggregation Consortium (ExAC) 0.00017
The Genome Aggregation Database (gnomAD), exomes 0.00019
Trans-Omics for Precision Medicine (TOPMed) 0.00010
Links
ClinGen: CA7648964
dbSNP: rs200814534
VarSome
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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 Jun 15, 2018 RCV000711890.5
Likely benign 1 criteria provided, single submitter Jun 4, 2020 RCV000245405.3
Likely benign 1 criteria provided, single submitter Dec 4, 2020 RCV001088501.2
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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
Likely benign
(Jun 04, 2020)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000320378.5
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (2)
Comment:
In silico models in agreement (benign);Other strong data supporting benign classification
Uncertain significance
(Jun 15, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Athena Diagnostics Inc
Accession: SCV000842301.1
Submitted: (Aug 31, 2018)
Evidence details
Publications
PubMed (2)
Uncertain significance
(Aug 23, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000620379.2
Submitted: (Jan 29, 2019)
Evidence details
Comment:
A variant of uncertain significance has been identified in the HCN4 gene. The F910L variant has been previously reported in at least two Spanish male … (more)
Likely benign
(Dec 04, 2020)
criteria provided, single submitter
Method: clinical testing
Brugada syndrome 8
Allele origin: germline
Invitae
Accession: SCV000541556.5
Submitted: (Jan 07, 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
Sudden Arrhythmic Death During Exercise: A Post-Mortem Genetic Analysis. Campuzano O Sports medicine (Auckland, N.Z.) 2017 PMID: 28255936
Natural and Undetermined Sudden Death: Value of Post-Mortem Genetic Investigation. Sanchez O PloS one 2016 PMID: 27930701

Text-mined citations for rs200814534...

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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