NM_000335.5(SCN5A):c.4769G>A (p.Trp1590Ter) AND Brugada syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 1, 2015
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:: RCV000201896.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.4769G>A (p.Trp1590Ter)]

NM_000335.5(SCN5A):c.4769G>A (p.Trp1590Ter)

Gene:

SCN5A:sodium voltage-gated channel alpha subunit 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000335.5(SCN5A):c.4769G>A (p.Trp1590Ter)

HGVS:

NC_000003.12:g.38554320C>T
NG_008934.1:g.100353G>A
NM_000335.5:c.4769G>AMANE SELECT
NM_001099404.2:c.4772G>A
NM_001099405.2:c.4718G>A
NM_001160160.2:c.4714+55G>A
NM_001160161.2:c.4610G>A
NM_001354701.2:c.4715G>A
NM_198056.3:c.4772G>A
NP_000326.2:p.Trp1590Ter
NP_001092874.1:p.Trp1591Ter
NP_001092875.1:p.Trp1573Ter
NP_001153633.1:p.Trp1537Ter
NP_001341630.1:p.Trp1572Ter
NP_932173.1:p.Trp1591Ter
NP_932173.1:p.Trp1591Ter
LRG_289t1:c.4772G>A
LRG_289:g.100353G>A
LRG_289p1:p.Trp1591Ter
NC_000003.11:g.38595811C>T
NM_198056.2:c.4772G>A

Protein change:

W1537*

Links:

dbSNP: rs863225273

NCBI 1000 Genomes Browser:

rs863225273

Molecular consequence:

NM_001160160.2:c.4714+55G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000335.5:c.4769G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001099404.2:c.4772G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001099405.2:c.4718G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001160161.2:c.4610G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354701.2:c.4715G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_198056.3:c.4772G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Brugada syndrome
Synonyms:: Sudden unexpected nocturnal death syndrome; Sudden unexplained nocturnal death syndrome; Sudden Unexplained Death Syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015263; MedGen: C1142166; OMIM: PS601144

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000256663	Agnes Ginges Centre for Molecular Cardiology, Centenary Institute	criteria provided, single submitter (Agnes Ginges Centre for Molecular Cardiology criteria (2015))	Pathogenic (Jul 1, 2015)	germline	research	PubMed (3) [See all records that cite these PMIDs] 20129283, 19251209, 15057319 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000256663

Agnes Ginges Centre for Molecular Cardiology, Centenary Institute

criteria provided, single submitter

(Agnes Ginges Centre for Molecular Cardiology criteria (2015))

Pathogenic
(Jul 1, 2015)

germline

research

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	1	not provided	not provided	not provided	research

Citations

PubMed

An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing.

Kapplinger JD, Tester DJ, Alders M, Benito B, Berthet M, Brugada J, Brugada P, Fressart V, Guerchicoff A, Harris-Kerr C, Kamakura S, Kyndt F, Koopmann TT, Miyamoto Y, Pfeiffer R, Pollevick GD, Probst V, Zumhagen S, Vatta M, Towbin JA, Shimizu W, Schulze-Bahr E, et al.

Heart Rhythm. 2010 Jan;7(1):33-46. doi: 10.1016/j.hrthm.2009.09.069. Epub 2009 Oct 8.

PubMed [citation]

PMID:: 20129283
PMCID:: PMC2822446

Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies.

Meregalli PG, Tan HL, Probst V, Koopmann TT, Tanck MW, Bhuiyan ZA, Sacher F, Kyndt F, Schott JJ, Albuisson J, Mabo P, Bezzina CR, Le Marec H, Wilde AA.

Heart Rhythm. 2009 Mar;6(3):341-8. doi: 10.1016/j.hrthm.2008.11.009. Epub 2008 Nov 11.

PubMed [citation]

PMID:: 19251209

See all PubMed Citations (3)

Details of each submission

From Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, SCV000256663.2

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

Description

The SCN5A Trp1591* variant was identified in our proband (an Asian male with Brugada syndrome). The proband presented with multiple syncopal episodes and was found to have spontaneous type 1 Brugada pattern. The SCN5A Trp1591* variant is absent from both the 1000 genomes project (http://www.1000genomes.org/), as well as the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/). The variant was identified in 1 unrelated individual with Brugada syndrome in an international consortium of SCN5A mutations (Kapplinger J. et al., 2010). Loss-of-function in SCN5A is well established as a mechanism of disease in Brugada syndrome (Baroudi G. et al., 2004). Therefore, we have classified this variant as "pathogenic".

#	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	1	not provided

Last Updated: Nov 5, 2022

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