NM_001037.5(SCN1B):c.448+321G>C AND Brugada syndrome 5

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 31, 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:: RCV000811781.8

Allele description [Variation Report for NM_001037.5(SCN1B):c.448+321G>C]

NM_001037.5(SCN1B):c.448+321G>C

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.448+321G>C

HGVS:

NC_000019.10:g.35034060G>C
NG_013359.1:g.8373G>C
NM_001037.5:c.448+321G>CMANE SELECT
NM_001321605.2:c.349+321G>C
NM_199037.5:c.769G>C
NP_950238.1:p.Gly257Arg
LRG_420t1:c.448+321G>C
LRG_420:g.8373G>C
NC_000019.9:g.35524964G>C
NM_199037.3:c.769G>C

Protein change:

G257R

Links:

dbSNP: rs72558028

NCBI 1000 Genomes Browser:

rs72558028

Molecular consequence:

NM_001037.5:c.448+321G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001321605.2:c.349+321G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_199037.5:c.769G>C - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000952067	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 31, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28837624, 21994374, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000952067

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 31, 2024)

germline

clinical testing

PubMed (3)
[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

Rare variants in genes encoding the cardiac sodium channel and associated compounds and their impact on outcome of catheter ablation of atrial fibrillation.

Husser D, Ueberham L, Hindricks G, Büttner P, Ingram C, Weeke P, Shoemaker MB, Adams V, Arya A, Sommer P, Darbar D, Roden DM, Bollmann A.

PLoS One. 2017;12(8):e0183690. doi: 10.1371/journal.pone.0183690.

PubMed [citation]

PMID:: 28837624
PMCID:: PMC5570360

Voltage-gated Na+ channel β1B: a secreted cell adhesion molecule involved in human epilepsy.

Patino GA, Brackenbury WJ, Bao Y, Lopez-Santiago LF, O'Malley HA, Chen C, Calhoun JD, Lafrenière RG, Cossette P, Rouleau GA, Isom LL.

J Neurosci. 2011 Oct 12;31(41):14577-91. doi: 10.1523/JNEUROSCI.0361-11.2011.

PubMed [citation]

PMID:: 21994374
PMCID:: PMC3212034

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000952067.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 257 of the SCN1B protein (p.Gly257Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with epilepsy (PMID: 21994374, 28837624). ClinVar contains an entry for this variant (Variation ID: 655577). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change affects SCN1B function (PMID: 21994374). 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.

#	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: Feb 25, 2025

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