NM_000335.5(SCN5A):c.3595dup (p.His1199fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 22, 2023
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:: RCV003574858.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.3595dup (p.His1199fs)]

NM_000335.5(SCN5A):c.3595dup (p.His1199fs)

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.3595dup (p.His1199fs)

HGVS:

NC_000003.12:g.38575366dup
NG_008934.1:g.79308dup
NM_000335.5:c.3595dupMANE SELECT
NM_001099404.2:c.3598dup
NM_001099405.2:c.3598dup
NM_001160160.2:c.3595dup
NM_001160161.2:c.3436dup
NM_001354701.2:c.3595dup
NM_198056.3:c.3598dup
NP_000326.2:p.His1199fs
NP_001092874.1:p.His1200fs
NP_001092875.1:p.His1200fs
NP_001153632.1:p.His1199fs
NP_001153633.1:p.His1146fs
NP_001341630.1:p.His1199fs
NP_932173.1:p.His1200fs
LRG_289t1:c.3598dup
LRG_289:g.79308dup
NC_000003.11:g.38616855_38616856insG
NC_000003.11:g.38616857dup
NM_198056.2:c.3598dup

Protein change:

H1146fs

Links:

dbSNP: rs1559745565

NCBI 1000 Genomes Browser:

rs1559745565

Molecular consequence:

NM_000335.5:c.3595dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001099404.2:c.3598dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001099405.2:c.3598dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001160160.2:c.3595dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001160161.2:c.3436dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354701.2:c.3595dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_198056.3:c.3598dup - 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
SCV004337477	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 22, 2023)	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

SCV004337477

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 22, 2023)

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, SCV004337477.1

#	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.His1200Profs*41) 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 variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 924057). 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: Oct 13, 2024

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