NM_000335.5(SCN5A):c.3960+1G>A AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 11, 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:: RCV000149447.3

Allele description [Variation Report for NM_000335.5(SCN5A):c.3960+1G>A]

NM_000335.5(SCN5A):c.3960+1G>A

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000335.5(SCN5A):c.3960+1G>A

HGVS:

NC_000003.12:g.38562414C>T
NG_008934.1:g.92259G>A
NM_000335.5:c.3960+1G>AMANE SELECT
NM_001099404.2:c.3963+1G>A
NM_001099405.2:c.3963+1G>A
NM_001160160.2:c.3960+1G>A
NM_001160161.2:c.3801+1G>A
NM_001354701.2:c.3960+1G>A
NM_198056.3:c.3963+1G>A
LRG_289t1:c.3963+1G>A
LRG_289:g.92259G>A
NC_000003.11:g.38603905C>T
NM_198056.2:c.3963+1G>A

Links:

dbSNP: rs483353016

NCBI 1000 Genomes Browser:

rs483353016

Molecular consequence:

NM_000335.5:c.3960+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001099404.2:c.3963+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001099405.2:c.3963+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001160160.2:c.3960+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001160161.2:c.3801+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354701.2:c.3960+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_198056.3:c.3963+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV000154202	Institute for Genetics of Heart Diseases, University Hospital Muenster	no assertion criteria provided	probable-pathogenic	not provided	not provided
SCV003525428	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 11, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 16199547, 20129283, 22789973, 10471492, 20031634, 24972929, 28341781, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000154202

Institute for Genetics of Heart Diseases, University Hospital Muenster

no assertion criteria provided

probable-pathogenic

not provided

SCV003525428

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 11, 2023)

germline

clinical testing

PubMed (8)
[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
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

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

See all PubMed Citations (8)

Details of each submission

From Institute for Genetics of Heart Diseases, University Hospital Muenster, SCV000154202.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	not provided	not provided

Description

Converted during submission to Likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not provided	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003525428.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 132906). This sequence change affects a donor splice site in intron 22 of the SCN5A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SCN5A are known to be pathogenic (PMID: 20129283, 22789973). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Disruption of this splice site has been observed in individuals with SCN5A-related conditions (PMID: 10471492, 20031634, 24972929, 28341781).

#	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: Sep 29, 2024

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