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NM_201596.3(CACNB2):c.1659G>C (p.Glu553Asp) AND Brugada syndrome 4

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 14, 2021
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:
RCV002934057.1

Allele description [Variation Report for NM_201596.3(CACNB2):c.1659G>C (p.Glu553Asp)]

NM_201596.3(CACNB2):c.1659G>C (p.Glu553Asp)

Gene:
CACNB2:calcium voltage-gated channel auxiliary subunit beta 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10p12.31
Genomic location:
Preferred name:
NM_201596.3(CACNB2):c.1659G>C (p.Glu553Asp)
HGVS:
  • NC_000010.11:g.18539400G>C
  • NG_016195.1:g.403724G>C
  • NM_000724.4:c.1494G>C
  • NM_001167945.2:c.1461G>C
  • NM_001330060.2:c.1380G>C
  • NM_001410882.1:c.1401G>C
  • NM_201570.3:c.1515G>C
  • NM_201571.4:c.1575G>C
  • NM_201572.4:c.1503G>C
  • NM_201590.3:c.1497G>C
  • NM_201593.3:c.1545G>C
  • NM_201596.3:c.1659G>CMANE SELECT
  • NM_201597.3:c.1587G>C
  • NP_000715.2:p.Glu498Asp
  • NP_001161417.1:p.Glu487Asp
  • NP_001316989.1:p.Glu460Asp
  • NP_001397811.1:p.Glu467Asp
  • NP_963864.1:p.Glu505Asp
  • NP_963865.2:p.Glu525Asp
  • NP_963866.2:p.Glu501Asp
  • NP_963884.2:p.Glu499Asp
  • NP_963887.2:p.Glu515Asp
  • NP_963890.2:p.Glu553Asp
  • NP_963891.1:p.Glu529Asp
  • LRG_381t1:c.1659G>C
  • LRG_381t2:c.1497G>C
  • LRG_381:g.403724G>C
  • LRG_381p1:p.Glu553Asp
  • LRG_381p2:p.Glu499Asp
  • NC_000010.10:g.18828329G>C
Protein change:
E460D
Molecular consequence:
  • NM_000724.4:c.1494G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001167945.2:c.1461G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330060.2:c.1380G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001410882.1:c.1401G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_201570.3:c.1515G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_201571.4:c.1575G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_201572.4:c.1503G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_201590.3:c.1497G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_201593.3:c.1545G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_201596.3:c.1659G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_201597.3:c.1587G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Brugada syndrome 4 (BRGDA4)
Identifiers:
MONDO: MONDO:0012743; MedGen: C2678477; Orphanet: 130; OMIM: 611876

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003278637Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 14, 2021) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Spectrum and prevalence of mutations involving BrS1- through BrS12-susceptibility genes in a cohort of unrelated patients referred for Brugada syndrome genetic testing: implications for genetic testing.

Crotti L, Marcou CA, Tester DJ, Castelletti S, Giudicessi JR, Torchio M, Medeiros-Domingo A, Simone S, Will ML, Dagradi F, Schwartz PJ, Ackerman MJ.

J Am Coll Cardiol. 2012 Oct 9;60(15):1410-8. doi: 10.1016/j.jacc.2012.04.037. Epub 2012 Jul 25.

PubMed [citation]
PMID:
22840528
PMCID:
PMC3624764

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, SCV003278637.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces glutamic acid with aspartic acid at codon 499 of the CACNB2 protein (p.Glu499Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs770237131, ExAC 0.009%). This missense change has been observed in individual(s) with clinical features of Brugada syndrome (PMID: 22840528). 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 C0"). 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: Feb 13, 2023