NM_000335.5(SCN5A):c.702del (p.Gly235_Leu236insTer) AND Brugada syndrome

delete

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 5, 2020
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:: RCV001206569.3

Allele description

NM_000335.5(SCN5A):c.702del (p.Gly235_Leu236insTer)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000335.5(SCN5A):c.702del (p.Gly235_Leu236insTer)

HGVS:

NC_000003.12:g.38613744del
NG_008934.1:g.40929del
NM_000335.5:c.702delMANE SELECT
NM_001099404.2:c.703+231del
NM_001099405.2:c.703+231del
NM_001160160.2:c.703+231del
NM_001160161.2:c.703+231del
NM_001354701.2:c.703+231del
NM_198056.3:c.702del
NP_000326.2:p.Gly235_Leu236insTer
NP_932173.1:p.Gly235_Leu236insTer
LRG_289t1:c.702del
LRG_289:g.40929del
NC_000003.11:g.38655235del
NM_198056.2:c.702del

Links:

dbSNP: rs2062156506

NCBI 1000 Genomes Browser:

rs2062156506

Molecular consequence:

NM_000335.5:c.702del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_198056.3:c.702del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001099404.2:c.703+231del - intron variant - [Sequence Ontology: SO:0001627]
NM_001099405.2:c.703+231del - intron variant - [Sequence Ontology: SO:0001627]
NM_001160160.2:c.703+231del - intron variant - [Sequence Ontology: SO:0001627]
NM_001160161.2:c.703+231del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354701.2:c.703+231del - intron variant - [Sequence Ontology: SO:0001627]

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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Tssr19457 AND (alive[prop]) (0)
Gene
Rattus norvegicus strain BN chromosome 18 CRA_213000034363124, whole genome shot...
Rattus norvegicus strain BN chromosome 18 CRA_213000034363124, whole genome shotgun sequence
gi|70507292|gb|AAHX01096502.1||gnl| AHX|CRA_213000034363124

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001377882	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 5, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20129283, 22789973, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001377882

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 5, 2020)

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

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

Brugada syndrome 2012.

Berne P, Brugada J.

Circ J. 2012;76(7):1563-71. Epub 2012 Jun 13. Review.

PubMed [citation]

PMID:: 22789973

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001377882.3

#	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 creates a premature translational stop signal (p.Leu236*) in the SCN5A gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN5A-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in SCN5A are known to be pathogenic (PMID: 20129283, 22789973). 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: Feb 7, 2023

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