NM_001037.5(SCN1B):c.632G>A (p.Cys211Tyr) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (6 submissions)
Last evaluated:: Jun 1, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000713013.47

Allele description [Variation Report for NM_001037.5(SCN1B):c.632G>A (p.Cys211Tyr)]

NM_001037.5(SCN1B):c.632G>A (p.Cys211Tyr)

Gene:

SCN1B:sodium voltage-gated channel beta subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.11

Genomic location:

Preferred name:

NM_001037.5(SCN1B):c.632G>A (p.Cys211Tyr)

Other names:

p.C211Y:TGC>TAC

HGVS:

NC_000019.10:g.35039676G>A
NG_013359.1:g.13989G>A
NM_001037.5:c.632G>AMANE SELECT
NM_001321605.2:c.533G>A
NP_001028.1:p.Cys211Tyr
NP_001308534.1:p.Cys178Tyr
LRG_420t1:c.632G>A
LRG_420:g.13989G>A
LRG_420p1:p.Cys211Tyr
NC_000019.9:g.35530580G>A
NM_001037.4:c.632G>A
NM_199037.2:c.*5578G>A
NM_199037.3:c.*5578G>A
Q07699:p.Cys211Tyr

Protein change:

C178Y

Links:

UniProtKB: Q07699#VAR_062527; dbSNP: rs150721582

NCBI 1000 Genomes Browser:

rs150721582

Molecular consequence:

NM_001037.5:c.632G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001321605.2:c.533G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000223621	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Benign (Dec 18, 2020)	germline	clinical testing	Citation Link,
SCV000340803	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (May 11, 2016)	germline	clinical testing	Citation Link,
SCV000843579	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Likely benign (Sep 20, 2017)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25253298, 27207958, 19522081, 26467025
SCV000886077	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Uncertain significance (Feb 27, 2018)	germline	clinical testing	Citation Link,
SCV001712983	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 14, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001746566	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely benign (Jun 1, 2024)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	5	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

SCN1B gene variants in Brugada Syndrome: a study of 145 SCN5A-negative patients.

Ricci MT, Menegon S, Vatrano S, Mandrile G, Cerrato N, Carvalho P, De Marchi M, Gaita F, Giustetto C, Giachino DF.

Sci Rep. 2014 Sep 25;4:6470. doi: 10.1038/srep06470.

PubMed [citation]

PMID:: 25253298
PMCID:: PMC5377327

Variants of Transient Receptor Potential Melastatin Member 4 in Childhood Atrioventricular Block.

Syam N, Chatel S, Ozhathil LC, Sottas V, Rougier JS, Baruteau A, Baron E, Amarouch MY, Daumy X, Probst V, Schott JJ, Abriel H.

J Am Heart Assoc. 2016 May 20;5(5). doi: 10.1161/JAHA.114.001625.

PubMed [citation]

PMID:: 27207958
PMCID:: PMC4889160

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000223621.12

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

Description

This variant is associated with the following publications: (PMID: 19522081, 31865891, 27207958, 25253298, 30821013)

#	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 Eurofins Ntd Llc (ga), SCV000340803.4

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

From Athena Diagnostics, SCV000843579.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

#	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 ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000886077.1

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

Description

The SCN1B c.632G>A; p.Cys211Tyr variant (rs150721582) has been reported in individuals diagnosed with Brugada syndrome, pediatric idiopathic epilepsy, and congenital atrioventricular block (Orrico 2009, Ricci 2014, Syam 2016), but was also detected in healthy control individuals (Orrico 2009). This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.04% (identified on 107 out of 277,166 chromosomes). The cysteine at position 211 is highly conserved, considering 12 species, and computational analyses of the effects of the p.Cys211Tyr variant on protein structure and function predict a deleterious effect (SIFT: damaging, PolyPhen-2: probably damaging). Based on the available information, the clinical significance of the p.Cys211Tyr variant cannot be determined with certainty.

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV001712983.1

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

From CeGaT Center for Human Genetics Tuebingen, SCV001746566.21

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	not provided

Description

SCN1B: PP3, BP5, BS2

#	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		5	not provided	not provided	not provided

Last Updated: Jan 13, 2025

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