NM_005477.3(HCN4):c.3229G>A (p.Gly1077Ser) AND Brugada syndrome 8

Clinical significance:Uncertain significance (Last evaluated: Oct 28, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001047439.1

Allele description [Variation Report for NM_005477.3(HCN4):c.3229G>A (p.Gly1077Ser)]

NM_005477.3(HCN4):c.3229G>A (p.Gly1077Ser)

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.3229G>A (p.Gly1077Ser)
HGVS:
  • NC_000015.10:g.73322864C>T
  • NG_009063.1:g.51401G>A
  • NM_005477.3:c.3229G>AMANE SELECT
  • NP_005468.1:p.Gly1077Ser
  • NC_000015.9:g.73615205C>T
  • NM_005477.2:c.3229G>A
Protein change:
G1077S
Molecular consequence:
  • NM_005477.3:c.3229G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Brugada syndrome 8 (BRGDA8)
Identifiers:
MONDO: MONDO:0013148; MedGen: C2751083; Orphanet: 130; OMIM: 613123

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001211400Invitaecriteria provided, single submitter
Uncertain significance
(Oct 28, 2019)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

A Distinct Cardiomyopathy: HCN4 Syndrome Comprising Myocardial Noncompaction, Bradycardia, Mitral Valve Defects, and Aortic Dilation.

Schweizer PA, Koenen M, Katus HA, Thomas D.

J Am Coll Cardiol. 2017 Mar 7;69(9):1209-1210. doi: 10.1016/j.jacc.2016.10.085. No abstract available.

PubMed [citation]
PMID:
28254188

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
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001211400.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces glycine with serine at codon 1077 of the HCN4 protein (p.Gly1077Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs746291340, ExAC 0.009%). This variant has been observed in an individual affected with dilated cardiomyopathy (PMID: 28254188) and in an individual affected with atrial fibrillation (PMID: 24607718). This variant has been reported not to substantially affect (PMID: 24607718) Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 7, 2021

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