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NM_005477.3(HCN4):c.1403C>T (p.Ala468Val) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 8, 2022
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:
RCV002393520.2

Allele description [Variation Report for NM_005477.3(HCN4):c.1403C>T (p.Ala468Val)]

NM_005477.3(HCN4):c.1403C>T (p.Ala468Val)

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.1403C>T (p.Ala468Val)
HGVS:
  • NC_000015.10:g.73329760G>A
  • NG_009063.1:g.44505C>T
  • NM_005477.3:c.1403C>TMANE SELECT
  • NP_005468.1:p.Ala468Val
  • NC_000015.9:g.73622101G>A
  • NM_005477.2:c.1403C>T
Protein change:
A468V
Links:
dbSNP: rs760413254
NCBI 1000 Genomes Browser:
rs760413254
Molecular consequence:
  • NM_005477.3:c.1403C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002702446Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Mar 8, 2022) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Next-generation sequencing of 100 candidate genes in young victims of suspected sudden cardiac death with structural abnormalities of the heart.

Hertz CL, Christiansen SL, Ferrero-Miliani L, Dahl M, Weeke PE; LuCamp., Ottesen GL, Frank-Hansen R, Bundgaard H, Morling N.

Int J Legal Med. 2016 Jan;130(1):91-102. doi: 10.1007/s00414-015-1261-8. Epub 2015 Sep 17.

PubMed [citation]
PMID:
26383259

Targeted panel sequencing in adult patients with left ventricular non-compaction reveals a large genetic heterogeneity.

Richard P, Ader F, Roux M, Donal E, Eicher JC, Aoutil N, Huttin O, Selton-Suty C, Coisne D, Jondeau G, Damy T, Mansencal N, Casalta AC, Michel N, Haentjens J, Faivre L, Lavoute C, Nguyen K, Tregouët DA, Habib G, Charron P.

Clin Genet. 2019 Mar;95(3):356-367. doi: 10.1111/cge.13484. Epub 2018 Dec 27.

PubMed [citation]
PMID:
30471092

Details of each submission

From Ambry Genetics, SCV002702446.2

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

Description

The p.A468V variant (also known as c.1403C>T), located in coding exon 4 of the HCN4 gene, results from a C to T substitution at nucleotide position 1403. The alanine at codon 468 is replaced by valine, an amino acid with similar properties. This alteration has been reported in a sudden cardiac death cohort, as well as a left ventricular non-compaction (LVNC) cohort (Hertz CL et al. Int J Legal Med, 2016 Jan;130:91-102; Richard P et al. Clin Genet, 2019 03;95:356-367). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. 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