NM_001037.5(SCN1B):c.518G>A (p.Trp173Ter) AND Brugada syndrome 5

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 22, 2022
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:: RCV002898924.3

Allele description [Variation Report for NM_001037.5(SCN1B):c.518G>A (p.Trp173Ter)]

NM_001037.5(SCN1B):c.518G>A (p.Trp173Ter)

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.518G>A (p.Trp173Ter)

HGVS:

NC_000019.10:g.35039186G>A
NG_013359.1:g.13499G>A
NM_001037.5:c.518G>AMANE SELECT
NM_001321605.2:c.419G>A
NP_001028.1:p.Trp173Ter
NP_001308534.1:p.Trp140Ter
LRG_420t1:c.518G>A
LRG_420:g.13499G>A
LRG_420p1:p.Trp173Ter
NC_000019.9:g.35530090G>A

Protein change:

W140*

Molecular consequence:

NM_001037.5:c.518G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001321605.2:c.419G>A - 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
SCV003237632	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 22, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17629415, 30660056, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003237632

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 22, 2022)

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

Generalized epilepsy with febrile seizures plus-associated sodium channel beta1 subunit mutations severely reduce beta subunit-mediated modulation of sodium channel function.

Xu R, Thomas EA, Gazina EV, Richards KL, Quick M, Wallace RH, Harkin LA, Heron SE, Berkovic SF, Scheffer IE, Mulley JC, Petrou S.

Neuroscience. 2007 Aug 10;148(1):164-74. Epub 2007 Jul 12.

PubMed [citation]

PMID:: 17629415

Sudden unexpected death in GEFS+ families with sodium channel pathogenic variants.

Myers KA, Shevell MI, Sébire G.

Epilepsy Res. 2019 Feb;150:66-69. doi: 10.1016/j.eplepsyres.2019.01.009. Epub 2019 Jan 14.

PubMed [citation]

PMID:: 30660056

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003237632.2

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SCN1B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp173*) in the SCN1B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SCN1B are known to be pathogenic (PMID: 17629415, 30660056). The SCN1B gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_001037.5, and corresponds to NM_199037.3:c.*5088G>A in the primary transcript.

#	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: Sep 29, 2024

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