NM_000335.5(SCN5A):c.3891dup (p.Ile1298fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 6, 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:: RCV003658607.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.3891dup (p.Ile1298fs)]

NM_000335.5(SCN5A):c.3891dup (p.Ile1298fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000335.5(SCN5A):c.3891dup (p.Ile1298fs)

HGVS:

NC_000003.12:g.38562487dup
NG_008934.1:g.92189dup
NM_000335.5:c.3891dupMANE SELECT
NM_001099404.2:c.3894dup
NM_001099405.2:c.3894dup
NM_001160160.2:c.3891dup
NM_001160161.2:c.3732dup
NM_001354701.2:c.3891dup
NM_198056.3:c.3894dup
NP_000326.2:p.Ile1298Hisfs
NP_000326.2:p.Ile1298fs
NP_001092874.1:p.Ile1299Hisfs
NP_001092874.1:p.Ile1299fs
NP_001092875.1:p.Ile1299fs
NP_001153632.1:p.Ile1298fs
NP_001153633.1:p.Ile1245fs
NP_001341630.1:p.Ile1298fs
NP_932173.1:p.Ile1299Hisfs
NP_932173.1:p.Ile1299fs
LRG_289t1:c.3891dup
LRG_289t2:c.3888dup
LRG_289t3:c.3891dup
LRG_289:g.92189dup
LRG_289p1:p.Ile1299Hisfs
LRG_289p2:p.Ile1298Hisfs
LRG_289p3:p.Ile1299Hisfs
NC_000003.11:g.38603974_38603975insG
NC_000003.11:g.38603978dup
NM_000335.4:c.3888dup
NM_001099404.1:c.3891dup
NM_198056.2:c.3891dup
NR_176299.1:n.4637dup

Protein change:

I1245fs

Molecular consequence:

NM_000335.5:c.3891dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001099404.2:c.3894dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001099405.2:c.3894dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001160160.2:c.3891dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001160161.2:c.3732dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354701.2:c.3891dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_198056.3:c.3894dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003326584	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 6, 2022)	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

SCV003326584

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 6, 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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003326584.2

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile1299Hisfs*20) 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).

#	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: Nov 3, 2024

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