NM_005477.3(HCN4):c.2730C>A (p.Phe910Leu) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Jun 15, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000711890.5

Allele description [Variation Report for NM_005477.3(HCN4):c.2730C>A (p.Phe910Leu)]

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

Gene:
HCN4:hyperpolarization activated cyclic nucleotide gated potassium channel 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q24.1
Genomic location:
Preferred name:
NM_005477.3(HCN4):c.2730C>A (p.Phe910Leu)
HGVS:
  • NC_000015.10:g.73323363G>T
  • NG_009063.1:g.50902C>A
  • NM_005477.3:c.2730C>AMANE SELECT
  • NP_005468.1:p.Phe910Leu
  • NC_000015.9:g.73615704G>T
  • NM_005477.2:c.2730C>A
Protein change:
F910L
Links:
dbSNP: rs200814534
NCBI 1000 Genomes Browser:
rs200814534
Molecular consequence:
  • NM_005477.3:c.2730C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000620379GeneDxcriteria provided, single submitter
Uncertain significance
(Aug 23, 2017)
germlineclinical testing

Citation Link,

SCV000842301Athena Diagnostics Inccriteria provided, single submitter
Uncertain significance
(Jun 15, 2018)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Natural and Undetermined Sudden Death: Value of Post-Mortem Genetic Investigation.

Sanchez O, Campuzano O, Fernández-Falgueras A, Sarquella-Brugada G, Cesar S, Mademont I, Mates J, Pérez-Serra A, Coll M, Pico F, Iglesias A, Tirón C, Allegue C, Carro E, Gallego MÁ, Ferrer-Costa C, Hospital A, Bardalet N, Borondo JC, Vingut A, Arbelo E, Brugada J, et al.

PLoS One. 2016;11(12):e0167358. doi: 10.1371/journal.pone.0167358. Erratum in: PLoS One. 2017 Feb 6;12 (2):e0171893.

PubMed [citation]
PMID:
27930701
PMCID:
PMC5145162

Sudden Arrhythmic Death During Exercise: A Post-Mortem Genetic Analysis.

Campuzano O, Sanchez-Molero O, Fernandez A, Mademont-Soler I, Coll M, Perez-Serra A, Mates J, Del Olmo B, Pico F, Nogue-Navarro L, Sarquella-Brugada G, Iglesias A, Cesar S, Carro E, Borondo JC, Brugada J, Castellà J, Medallo J, Brugada R.

Sports Med. 2017 Oct;47(10):2101-2115. doi: 10.1007/s40279-017-0705-3.

PubMed [citation]
PMID:
28255936
See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000620379.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

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 individuals with sudden cardiac death occurring in their 40's (Sanchez et al., 2016; Campuzano et al., 2017); however, no family history details or segregation studies were reported. This variant is observed in 2/1014 (0.20%) alleles from individuals of Latino ancestry, and in 3/15912 (0.02%) alleles from individuals of Non-Finnish European ancestry, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Additionally, although this substitution occurs at a position that is conserved in mammals, F910L is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Lastly, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Athena Diagnostics Inc, SCV000842301.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2021

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