NM_000335.5(SCN5A):c.4296+1del AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 17, 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:: RCV003542346.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.4296+1del]

NM_000335.5(SCN5A):c.4296+1del

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.4296+1del

HGVS:

NC_000003.12:g.38557235del
NG_008934.1:g.97443del
NM_000335.5:c.4296+1delMANE SELECT
NM_001099404.2:c.4299+1del
NM_001099405.2:c.4246-652del
NM_001160160.2:c.4296+1del
NM_001160161.2:c.4137+1del
NM_001354701.2:c.4243-652del
NM_198056.3:c.4299+1del
LRG_289t1:c.4299+1del
LRG_289t3:c.4299+1del
LRG_289:g.97443del
NC_000003.11:g.38598721del
NC_000003.11:g.38598726del
NM_001099404.1:c.4299+1del
NM_198056.2:c.4299+1delG

Links:

dbSNP: rs1450434935

NCBI 1000 Genomes Browser:

rs1450434935

Molecular consequence:

NM_001099405.2:c.4246-652del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354701.2:c.4243-652del - intron variant - [Sequence Ontology: SO:0001627]
NM_000335.5:c.4296+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001099404.2:c.4299+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001160160.2:c.4296+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001160161.2:c.4137+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_198056.3:c.4299+1del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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JGI_CAAJ16107.rev NIH_XGC_tropBrn2 Xenopus tropicalis cDNA clone IMAGE:7645846 3...
JGI_CAAJ16107.rev NIH_XGC_tropBrn2 Xenopus tropicalis cDNA clone IMAGE:7645846 3', mRNA sequence
gi|71461193|gnl|dbEST|30354501|gb|C 86.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003525426	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 17, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 20129283, 22789973, 19251209, 29447731, 30193851, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003525426

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 17, 2022)

germline

clinical testing

PubMed (6)
[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 (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003525426.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr1434Metfs*29) in the SCN5A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SCN5A are known to be pathogenic (PMID: 20129283, 22789973). This premature translational stop signal has been observed in individual(s) with Brugada syndrome and/or noncompaction cardiomyopathy (PMID: 19251209, 29447731, 30193851). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1327132).

#	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: Oct 26, 2024

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