NM_000335.5(SCN5A):c.5390G>A (p.Trp1797Ter) AND Brugada syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 27, 2019
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:: RCV004018075.1

Allele description [Variation Report for NM_000335.5(SCN5A):c.5390G>A (p.Trp1797Ter)]

NM_000335.5(SCN5A):c.5390G>A (p.Trp1797Ter)

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.5390G>A (p.Trp1797Ter)

HGVS:

NC_000003.12:g.38550979C>T
NG_008934.1:g.103694G>A
NM_000335.5:c.5390G>AMANE SELECT
NM_001099404.2:c.5393G>A
NM_001099405.2:c.5339G>A
NM_001160160.2:c.5294G>A
NM_001160161.2:c.5231G>A
NM_001354701.2:c.5336G>A
NM_198056.3:c.5393G>A
NP_000326.2:p.Trp1797Ter
NP_000326.2:p.Trp1797Ter
NP_001092874.1:p.Trp1798Ter
NP_001092874.1:p.Trp1798Ter
NP_001092875.1:p.Trp1780Ter
NP_001153632.1:p.Trp1765Ter
NP_001153633.1:p.Trp1744Ter
NP_001341630.1:p.Trp1779Ter
NP_932173.1:p.Trp1798Ter
NP_932173.1:p.Trp1798Ter
LRG_289t1:c.5393G>A
LRG_289t2:c.5390G>A
LRG_289t3:c.5393G>A
LRG_289:g.103694G>A
LRG_289p1:p.Trp1798Ter
LRG_289p2:p.Trp1797Ter
LRG_289p3:p.Trp1798Ter
NC_000003.11:g.38592470C>T
NM_000335.4:c.5390G>A
NM_001099404.1:c.5393G>A
NM_198056.2:c.5393G>A
NR_176299.1:n.6139G>A

Protein change:

W1744*

Molecular consequence:

NR_176299.1:n.6139G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000335.5:c.5390G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001099404.2:c.5393G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001099405.2:c.5339G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001160160.2:c.5294G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001160161.2:c.5231G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354701.2:c.5336G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_198056.3:c.5393G>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
SCV004847653	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Pathogenic (Mar 27, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19716085, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004847653

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Pathogenic
(Mar 27, 2019)

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

Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.

Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, Wilde AA, Ackerman MJ.

Heart Rhythm. 2009 Sep;6(9):1297-303. doi: 10.1016/j.hrthm.2009.05.021. Epub 2009 Jun 23.

PubMed [citation]

PMID:: 19716085
PMCID:: PMC3049907

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004847653.1

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

Description

The p.Trp1798X variant in SCN5A has been reported in 1 individual referred for LQTS genetic testing (Kapplinger 2009). It was absent from large population studies. This nonsense variant leads to a premature termination codon at position 1798. This alteration occurs within the last exon and is, therefore, likely to escape nonsense mediated decay (NMD) and result in a truncated protein. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant Brugada syndrome. ACMG/AMP Criteria applied: PVS1_Strong, PM2.

#	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 1, 2024

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