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NM_005477.3(HCN4):c.3134C>T (p.Ala1045Val) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 23, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002325525.3

Allele description [Variation Report for NM_005477.3(HCN4):c.3134C>T (p.Ala1045Val)]

NM_005477.3(HCN4):c.3134C>T (p.Ala1045Val)

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.3134C>T (p.Ala1045Val)
HGVS:
  • NC_000015.10:g.73322959G>A
  • NG_009063.1:g.51306C>T
  • NM_005477.3:c.3134C>TMANE SELECT
  • NP_005468.1:p.Ala1045Val
  • NC_000015.9:g.73615300G>A
  • NM_005477.2:c.3134C>T
Protein change:
A1045V
Links:
dbSNP: rs980750316
NCBI 1000 Genomes Browser:
rs980750316
Molecular consequence:
  • NM_005477.3:c.3134C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002607464Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Feb 23, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

A novel trafficking-defective HCN4 mutation is associated with early-onset atrial fibrillation.

Macri V, Mahida SN, Zhang ML, Sinner MF, Dolmatova EV, Tucker NR, McLellan M, Shea MA, Milan DJ, Lunetta KL, Benjamin EJ, Ellinor PT.

Heart Rhythm. 2014 Jun;11(6):1055-1062. doi: 10.1016/j.hrthm.2014.03.002. Epub 2014 Mar 4.

PubMed [citation]
PMID:
24607718
PMCID:
PMC4130372

Pacemaker activity of the human sinoatrial node: an update on the effects of mutations in HCN4 on the hyperpolarization-activated current.

Verkerk AO, Wilders R.

Int J Mol Sci. 2015 Jan 29;16(2):3071-94. doi: 10.3390/ijms16023071. Review.

PubMed [citation]
PMID:
25642760
PMCID:
PMC4346881

Details of each submission

From Ambry Genetics, SCV002607464.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The p.A1045V variant (also known as c.3134C>T), located in coding exon 8 of the HCN4 gene, results from a C to T substitution at nucleotide position 3134. The alanine at codon 1045 is replaced by valine, an amino acid with similar properties. This variant was reported in an individual from the Framingham Heart Study cohort; however clinical details were limited (Macri V et al. Heart Rhythm, 2014 Jun;11:1055-1062). Limited electrophysiology studies have not shown this variant to have a significant functional impact (Macri V et al. Heart Rhythm, 2014 Jun;11:1055-1062; Verkerk AO et al. Int J Mol Sci, 2015 Jan;16:3071-94). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Sep 29, 2024