NM_001037.5(SCN1B):c.295A>T (p.Lys99Ter) AND Brugada syndrome 5

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 17, 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:: RCV002842946.4

Allele description [Variation Report for NM_001037.5(SCN1B):c.295A>T (p.Lys99Ter)]

NM_001037.5(SCN1B):c.295A>T (p.Lys99Ter)

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.295A>T (p.Lys99Ter)

HGVS:

NC_000019.10:g.35033586A>T
NG_013359.1:g.7899A>T
NM_001037.4:c.295A>T
NM_001037.5:c.295A>TMANE SELECT
NM_001321605.2:c.196A>T
NM_199037.5:c.295A>T
NP_001028.1:p.Lys99Ter
NP_001308534.1:p.Lys66Ter
NP_950238.1:p.Lys99Ter
LRG_420t1:c.295A>T
LRG_420:g.7899A>T
LRG_420p1:p.Lys99Ter
NC_000019.9:g.35524490A>T

Protein change:

K66*

Links:

dbSNP: rs1555720728

NCBI 1000 Genomes Browser:

rs1555720728

Molecular consequence:

NM_001037.5:c.295A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001321605.2:c.196A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_199037.5:c.295A>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV003215444	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 17, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18464934, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003215444

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 17, 2024)

germline

clinical testing

PubMed (2)
[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

Sodium channel β1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans.

Watanabe H, Koopmann TT, Le Scouarnec S, Yang T, Ingram CR, Schott JJ, Demolombe S, Probst V, Anselme F, Escande D, Wiesfeld AC, Pfeufer A, Kääb S, Wichmann HE, Hasdemir C, Aizawa Y, Wilde AA, Roden DM, Bezzina CR.

J Clin Invest. 2008 Jun;118(6):2260-8. doi: 10.1172/JCI33891.

PubMed [citation]

PMID:: 18464934
PMCID:: PMC2373423

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003215444.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Lys99*) in the SCN1B gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 170 amino acid(s) of the SCN1B protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 2010128). This variant disrupts a region of the SCN1B protein in which other variant(s) (p.Trp179*) have been determined to be pathogenic (PMID: 18464934; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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: May 16, 2025

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