NM_001037.5(SCN1B):c.363C>G (p.Cys121Trp) AND Brugada syndrome 5

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 25, 2024
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:: RCV000646741.14

Allele description [Variation Report for NM_001037.5(SCN1B):c.363C>G (p.Cys121Trp)]

NM_001037.5(SCN1B):c.363C>G (p.Cys121Trp)

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.363C>G (p.Cys121Trp)

Other names:

p.C121W:TGC>TGG

HGVS:

NC_000019.10:g.35033654C>G
NG_013359.1:g.7967C>G
NM_001037.5:c.363C>GMANE SELECT
NM_001321605.2:c.264C>G
NM_199037.5:c.363C>G
NP_001028.1:p.Cys121Trp
NP_001308534.1:p.Cys88Trp
NP_950238.1:p.Cys121Trp
LRG_420t1:c.363C>G
LRG_420:g.7967C>G
LRG_420p1:p.Cys121Trp
NC_000019.9:g.35524558C>G
NM_001037.3:c.363C>G
NM_001037.4:c.363C>G
NM_199037.3:c.363C>G
Q07699:p.Cys121Trp

Protein change:

C121W; CYS121TRP

Links:

UniProtKB: Q07699#VAR_010165; OMIM: 600235.0001; dbSNP: rs104894718

NCBI 1000 Genomes Browser:

rs104894718

Molecular consequence:

NM_001037.5:c.363C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001321605.2:c.264C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_199037.5:c.363C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Brugada syndrome 5 (BRGDA5)
Identifiers:: MONDO: MONDO:0013015; MedGen: C2748541; Orphanet: 130; Orphanet: 871; OMIM: 612838

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GSE261395[ACCN] AND gsm[ETYP] (21)
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Mus musculus 16 days embryo head cDNA, RIKEN full-length enriched library, clone:C130012P16 product:inferred: special AT-rich sequence binding protein 1, full insert sequence
gi|26099889|dbj|AK081385.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000768526	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 25, 2024)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 9697698, 12011299, 17020904, 20628201, 25421039, 27277800, 28331474, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000768526

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 25, 2024)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

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

Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B.

Wallace RH, Wang DW, Singh R, Scheffer IE, George AL Jr, Phillips HA, Saar K, Reis A, Johnson EW, Sutherland GR, Berkovic SF, Mulley JC.

Nat Genet. 1998 Aug;19(4):366-70.

PubMed [citation]

PMID:: 9697698

Generalized epilepsy with febrile seizures plus: mutation of the sodium channel subunit SCN1B.

Wallace RH, Scheffer IE, Parasivam G, Barnett S, Wallace GB, Sutherland GR, Berkovic SF, Mulley JC.

Neurology. 2002 May 14;58(9):1426-9.

PubMed [citation]

PMID:: 12011299

See all PubMed Citations (8)

Details of each submission

From Invitae, SCV000768526.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 121 of the SCN1B protein (p.Cys121Trp). This variant is present in population databases (rs104894718, gnomAD 0.003%). This missense change has been observed in individual(s) with autosomal dominant SCN1B-related conditions (PMID: 9697698, 12011299, 17020904). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 9252). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects SCN1B function (PMID: 20628201, 25421039, 27277800, 28331474). For these reasons, this variant has been classified as Pathogenic.

#	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: Jun 2, 2024

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