NM_005477.3(HCN4):c.1123C>T (p.Arg375Cys) AND Brugada syndrome 8

Clinical significance:Uncertain significance (Last evaluated: Nov 15, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000693215.2

Allele description [Variation Report for NM_005477.3(HCN4):c.1123C>T (p.Arg375Cys)]

NM_005477.3(HCN4):c.1123C>T (p.Arg375Cys)

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.1123C>T (p.Arg375Cys)
HGVS:
  • NC_000015.10:g.73343471G>A
  • NG_009063.1:g.30794C>T
  • NM_005477.3:c.1123C>TMANE SELECT
  • NP_005468.1:p.Arg375Cys
  • NC_000015.9:g.73635812G>A
  • NM_005477.2:c.1123C>T
Protein change:
R375C
Links:
dbSNP: rs755356387
NCBI 1000 Genomes Browser:
rs755356387
Molecular consequence:
  • NM_005477.3:c.1123C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000821075Invitaecriteria provided, single submitter
Uncertain significance
(Nov 15, 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 fast and cost-effective molecular diagnostic tool for genetic diseases involved in sudden cardiac death.

Chanavat V, Janin A, Millat G.

Clin Chim Acta. 2016 Jan 30;453:80-5. doi: 10.1016/j.cca.2015.12.011. Epub 2015 Dec 10.

PubMed [citation]
PMID:
26688388

Functional reclassification of variants of uncertain significance in the HCN4 gene identified in sudden unexpected death.

Dong J, Subbotina E, Williams N, Sampson BA, Tang Y, Coetzee WA.

Pacing Clin Electrophysiol. 2019 Feb;42(2):275-282. doi: 10.1111/pace.13593. Epub 2019 Jan 4.

PubMed [citation]
PMID:
30578647
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000821075.3

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

Description

This sequence change replaces arginine with cysteine at codon 375 of the HCN4 protein (p.Arg375Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs755356387, ExAC 0.001%). This variant has been observed in individual(s) with left ventricular noncompaction or sudden unexplained death (PMID: 26688388, 30578647). ClinVar contains an entry for this variant (Variation ID: 571947). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C). 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. 5

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

Last Updated: Oct 7, 2021

Support Center