NM_201596.3(CACNB2):c.1670C>T (p.Ser557Leu) AND Brugada syndrome 4

Germline classification:: Benign/Likely benign (4 submissions)
Last evaluated:: Jan 26, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000458519.30

Allele description [Variation Report for NM_201596.3(CACNB2):c.1670C>T (p.Ser557Leu)]

NM_201596.3(CACNB2):c.1670C>T (p.Ser557Leu)

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.1670C>T (p.Ser557Leu)

Other names:

p.S502L:TCG>TTG

HGVS:

NC_000010.11:g.18539411C>T
NG_016195.1:g.403735C>T
NM_000724.4:c.1505C>T
NM_001167945.2:c.1472C>T
NM_001330060.2:c.1391C>T
NM_201570.3:c.1526C>T
NM_201571.4:c.1586C>T
NM_201572.4:c.1514C>T
NM_201590.3:c.1508C>T
NM_201593.3:c.1556C>T
NM_201596.3:c.1670C>TMANE SELECT
NM_201597.3:c.1598C>T
NP_000715.2:p.Ser502Leu
NP_001161417.1:p.Ser491Leu
NP_001316989.1:p.Ser464Leu
NP_963864.1:p.Ser509Leu
NP_963865.2:p.Ser529Leu
NP_963866.2:p.Ser505Leu
NP_963884.2:p.Ser503Leu
NP_963887.2:p.Ser519Leu
NP_963890.2:p.Ser557Leu
NP_963891.1:p.Ser533Leu
LRG_381t1:c.1670C>T
LRG_381t2:c.1508C>T
LRG_381:g.403735C>T
LRG_381p1:p.Ser557Leu
LRG_381p2:p.Ser503Leu
NC_000010.10:g.18828340C>T
NM_000724.3:c.1505C>T
NM_201590.2:c.1508C>T

Protein change:

S464L

Links:

dbSNP: rs137886839

NCBI 1000 Genomes Browser:

rs137886839

Molecular consequence:

NM_000724.4:c.1505C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001167945.2:c.1472C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330060.2:c.1391C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_201570.3:c.1526C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_201571.4:c.1586C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_201572.4:c.1514C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_201590.3:c.1508C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_201593.3:c.1556C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_201596.3:c.1670C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_201597.3:c.1598C>T - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000562848	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 26, 2025)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000743845	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus	criteria provided, single submitter (ACGS Guidelines, 2013)	Benign (Oct 13, 2017)	germline	clinical testing	Citation Link,
SCV001159102	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Likely benign (Jul 24, 2018)	germline	clinical testing	Citation Link,
SCV002796724	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Sep 30, 2021)	unknown	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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000562848.10

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

#	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

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV000743845.1

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

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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001159102.1

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

#	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

From Fulgent Genetics, Fulgent Genetics, SCV002796724.1

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

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

Last Updated: Jun 29, 2025

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