NM_000335.5(SCN5A):c.4654del (p.Ser1552fs) AND Brugada syndrome

delete

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 4, 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:: RCV000706176.2

Allele description

NM_000335.5(SCN5A):c.4654del (p.Ser1552fs)

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.4654del (p.Ser1552fs)

HGVS:

NC_000003.12:g.38554437del
NG_008934.1:g.100238del
NM_000335.5:c.4654delMANE SELECT
NM_001099404.2:c.4657del
NM_001099405.2:c.4603del
NM_001160160.2:c.4654del
NM_001160161.2:c.4495del
NM_001354701.2:c.4600del
NM_198056.3:c.4657del
NP_000326.2:p.Ser1552fs
NP_001092874.1:p.Ser1553fs
NP_001092875.1:p.Ser1535fs
NP_001153632.1:p.Ser1552fs
NP_001153633.1:p.Ser1499fs
NP_001341630.1:p.Ser1534fs
NP_932173.1:p.Ser1553fs
LRG_289:g.100238del
NC_000003.11:g.38595926del
NC_000003.11:g.38595928del
NM_198056.2:c.4657delA

Protein change:

S1499fs

Links:

dbSNP: rs1559725687

NCBI 1000 Genomes Browser:

rs1559725687

Molecular consequence:

NM_000335.5:c.4654del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001099404.2:c.4657del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001099405.2:c.4603del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001160160.2:c.4654del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001160161.2:c.4495del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354701.2:c.4600del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_198056.3:c.4657del - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000835213	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 4, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17897635, 18361072, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000835213

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 4, 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

A novel C-terminal truncation SCN5A mutation from a patient with sick sinus syndrome, conduction disorder and ventricular tachycardia.

Tan BH, Iturralde-Torres P, Medeiros-Domingo A, Nava S, Tester DJ, Valdivia CR, Tusié-Luna T, Ackerman MJ, Makielski JC.

Cardiovasc Res. 2007 Dec 1;76(3):409-17. Epub 2007 Aug 22.

PubMed [citation]

PMID:: 17897635
PMCID:: PMC2100438

A novel SCN5A deletion mutation in a child with ventricular tachycardia, recurrent aborted sudden death, and Brugada electrocardiographic pattern.

Márquez MF, Cruz-Robles D, Inés-Real S, Gallardo GJ, Gonzlez-Hermosillo A, Cárdenas M, Vargas-Alarcón G.

Arch Cardiol Mex. 2007 Oct-Dec;77(4):284-7.

PubMed [citation]

PMID:: 18361072

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000835213.2

#	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.Ser1553Valfs*78) in the SCN5A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 464 amino acid(s) of the SCN5A 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 SCN5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 582177). This variant disrupts a region of the SCN5A protein in which other variant(s) (p.Glu1823Hisfs*10) have been determined to be pathogenic (PMID: 17897635, 18361072; 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: Feb 7, 2023

ClinVar

Relating variation to medicine