NM_005477.3(HCN4):c.3495_3498del (p.Ser1166fs) AND Brugada syndrome 8

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 22, 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:: RCV001874357.4

Allele description [Variation Report for NM_005477.3(HCN4):c.3495_3498del (p.Ser1166fs)]

NM_005477.3(HCN4):c.3495_3498del (p.Ser1166fs)

Gene:

HCN4:hyperpolarization activated cyclic nucleotide gated potassium channel 4 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

15q24.1

Genomic location:

Preferred name:

NM_005477.3(HCN4):c.3495_3498del (p.Ser1166fs)

HGVS:

NC_000015.10:g.73322598_73322601del
NG_009063.1:g.51667_51670del
NM_005477.3:c.3495_3498delMANE SELECT
NP_005468.1:p.Ser1166fs
NC_000015.9:g.73614936_73614939del
NC_000015.9:g.73614939_73614942del

Protein change:

S1166fs

Links:

dbSNP: rs2151213747

NCBI 1000 Genomes Browser:

rs2151213747

Molecular consequence:

NM_005477.3:c.3495_3498del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002133354	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 22, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002133354

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 22, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002133354.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1368247). This variant has not been reported in the literature in individuals affected with HCN4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser1166Cysfs*14) in the HCN4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 38 amino acid(s) of the HCN4 protein.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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