NM_000335.5(SCN5A):c.4179C>G (p.Tyr1393Ter) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 6, 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:: RCV002327048.3

Allele description [Variation Report for NM_000335.5(SCN5A):c.4179C>G (p.Tyr1393Ter)]

NM_000335.5(SCN5A):c.4179C>G (p.Tyr1393Ter)

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.4179C>G (p.Tyr1393Ter)

HGVS:

NC_000003.12:g.38560210G>C
NG_008934.1:g.94463C>G
NM_000335.5:c.4179C>GMANE SELECT
NM_001099404.2:c.4182C>G
NM_001099405.2:c.4182C>G
NM_001160160.2:c.4179C>G
NM_001160161.2:c.4020C>G
NM_001354701.2:c.4179C>G
NM_198056.3:c.4182C>G
NP_000326.2:p.Tyr1393Ter
NP_001092874.1:p.Tyr1394Ter
NP_001092875.1:p.Tyr1394Ter
NP_001153632.1:p.Tyr1393Ter
NP_001153633.1:p.Tyr1340Ter
NP_001341630.1:p.Tyr1393Ter
NP_932173.1:p.Tyr1394Ter
NP_932173.1:p.Tyr1394Ter
LRG_289t1:c.4182C>G
LRG_289:g.94463C>G
LRG_289p1:p.Tyr1394Ter
NC_000003.11:g.38601701G>C
NM_198056.2:c.4182C>G

Protein change:

Y1340*

Links:

dbSNP: rs863224532

NCBI 1000 Genomes Browser:

rs863224532

Molecular consequence:

NM_000335.5:c.4179C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001099404.2:c.4182C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001099405.2:c.4182C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001160160.2:c.4179C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001160161.2:c.4020C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354701.2:c.4179C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_198056.3:c.4182C>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002628492	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 6, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20129283, 30662450 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002628492

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 6, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Impact of Ancestral Differences and Reassessment of the Classification of Previously Reported Pathogenic Variants in Patients With Brugada Syndrome in the Genomic Era: A SADS-TW BrS Registry.

Chen CJ, Lu TP, Lin LY, Liu YB, Ho LT, Huang HC, Lai LP, Hwang JJ, Yeh SS, Wu CK, Juang JJ, Antzelevitch C.

Front Genet. 2018;9:680. doi: 10.3389/fgene.2018.00680.

PubMed [citation]

PMID:: 30662450
PMCID:: PMC6328444

Details of each submission

From Ambry Genetics, SCV002628492.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.Y1394* pathogenic mutation (also known as c.4182C>G), located in coding exon 22 of the SCN5A gene, results from a C to G substitution at nucleotide position 4182. This changes the amino acid from a tyrosine to a stop codon within coding exon 22. This mutation has been detected in an individual with clinically suspected Brugada syndrome (Kapplinger JD et al. Heart Rhythm, 2010 Jan;7:33-46). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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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