NM_005477.3(HCN4):c.2420G>A (p.Arg807His) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Mar 27, 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:
RCV000711884.3

Allele description [Variation Report for NM_005477.3(HCN4):c.2420G>A (p.Arg807His)]

NM_005477.3(HCN4):c.2420G>A (p.Arg807His)

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.2420G>A (p.Arg807His)
HGVS:
  • NC_000015.10:g.73323673C>T
  • NG_009063.1:g.50592G>A
  • NM_005477.3:c.2420G>AMANE SELECT
  • NP_005468.1:p.Arg807His
  • NC_000015.9:g.73616014C>T
  • NM_005477.2:c.2420G>A
Protein change:
R807H
Links:
dbSNP: rs200395062
NCBI 1000 Genomes Browser:
rs200395062
Molecular consequence:
  • NM_005477.3:c.2420G>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
SCV000589981GeneDxcriteria provided, single submitter
Uncertain significance
(May 11, 2017)
germlineclinical testing

Citation Link,

SCV000842295Athena Diagnostics Inccriteria provided, single submitter
Uncertain significance
(Mar 27, 2018)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

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

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317

Details of each submission

From GeneDx, SCV000589981.3

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

Description

A variant of uncertain significance has been identified in the HCN4 gene. The R807H variant has not been published as pathogenic or been reported as benign to our knowledge. This variant has been observed in 3/6060 (0.05%) alleles from individuals of Finnish European ancestry, and in 7/62738 (0.01%) 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). The R807H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, this substitution occurs at a position where amino acids with similar properties to arginine (R) are tolerated across species, and histidine (H) is the wild-type residue at this position in multiple non-mammalian species. Finally, 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, SCV000842295.1

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

Last Updated: Oct 8, 2021

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