NM_005477.3(HCN4):c.2809C>T (p.Gln937Ter) AND Brugada syndrome 8

Clinical significance:Uncertain significance (Last evaluated: Apr 5, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_005477.3(HCN4):c.2809C>T (p.Gln937Ter)]

NM_005477.3(HCN4):c.2809C>T (p.Gln937Ter)

HCN4:hyperpolarization activated cyclic nucleotide gated potassium channel 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_005477.3(HCN4):c.2809C>T (p.Gln937Ter)
  • NC_000015.10:g.73323284G>A
  • NG_009063.1:g.50981C>T
  • NM_005477.3:c.2809C>TMANE SELECT
  • NP_005468.1:p.Gln937Ter
  • NC_000015.9:g.73615625G>A
  • NM_005477.2:c.2809C>T
Protein change:
Molecular consequence:
  • NM_005477.3:c.2809C>T - nonsense - [Sequence Ontology: SO:0001587]


Brugada syndrome 8 (BRGDA8)
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)
SCV001219890Invitaecriteria provided, single submitter
Uncertain significance
(Apr 5, 2019)
germlineclinical testing

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

Summary from all submissions

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



Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

Details of each submission

From Invitae, SCV001219890.2

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


This sequence change results in a premature translational stop signal in the HCN4 gene (p.Gln937*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 267 amino acids of the HCN4 protein. This variant is present in population databases (rs776757023, ExAC 0.009%). This variant has not been reported in the literature in individuals with HCN4-related conditions. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. 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.

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

Last Updated: Oct 7, 2021

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