NM_005477.3(HCN4):c.82G>A (p.Glu28Lys) AND Brugada syndrome 8

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 10, 2017
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:: RCV000532717.6

Allele description [Variation Report for NM_005477.3(HCN4):c.82G>A (p.Glu28Lys)]

NM_005477.3(HCN4):c.82G>A (p.Glu28Lys)

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.82G>A (p.Glu28Lys)

HGVS:

NC_000015.10:g.73368189C>T
NG_009063.1:g.6076G>A
NM_005477.3:c.82G>AMANE SELECT
NP_005468.1:p.Glu28Lys
NC_000015.9:g.73660530C>T
NM_005477.2:c.82G>A

Protein change:

E28K

Links:

dbSNP: rs867068803

NCBI 1000 Genomes Browser:

rs867068803

Molecular consequence:

NM_005477.3:c.82G>A - 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

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acyl-CoA-binding domain-containing protein 4 isoform X2 [Glycine max]
acyl-CoA-binding domain-containing protein 4 isoform X2 [Glycine max]
gi|2027513741|ref|XP_040865893.1|

Protein
enoyl-CoA hydratase-related protein [Clostridium kluyveri]
enoyl-CoA hydratase-related protein [Clostridium kluyveri]
gi|501051242|ref|WP_012102871.1|

Protein
BarcodingPTplants
BarcodingPTplants
DNA barcoding, aromatic, medicinal, and condiment plants from Portugal

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000648472	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 10, 2017)	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

SCV000648472

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 10, 2017)

germline

clinical testing

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

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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 Invitae, SCV000648472.4

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

Description

In summary, this variant has uncertain impact on HCN4 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with a HCN4-related disease. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces glutamic acid with lysine at codon 28 of the HCN4 protein (p.Glu28Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine.

#	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 16, 2024

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