NM_000335.5(SCN5A):c.1890G>A (p.Thr630=) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 11, 2024
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:: RCV000618308.14

Allele description [Variation Report for NM_000335.5(SCN5A):c.1890G>A (p.Thr630=)]

NM_000335.5(SCN5A):c.1890G>A (p.Thr630=)

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.1890G>A (p.Thr630=)

HGVS:

NC_000003.12:g.38603712C>T
NG_008934.1:g.50961G>A
NM_000335.5:c.1890G>AMANE SELECT
NM_001099404.2:c.1890G>A
NM_001099405.2:c.1890G>A
NM_001160160.2:c.1890G>A
NM_001160161.2:c.1890G>A
NM_001354701.2:c.1890G>A
NM_198056.3:c.1890G>A
NP_000326.2:p.Thr630=
NP_001092874.1:p.Thr630=
NP_001092875.1:p.Thr630=
NP_001153632.1:p.Thr630=
NP_001153633.1:p.Thr630=
NP_001341630.1:p.Thr630=
NP_932173.1:p.Thr630=
NP_932173.1:p.Thr630=
LRG_289t1:c.1890G>A
LRG_289:g.50961G>A
LRG_289p1:p.Thr630=
NC_000003.11:g.38645203C>T
NM_198056.2:c.1890G>A
p.Thr630Thr

Links:

dbSNP: rs1204915217

NCBI 1000 Genomes Browser:

rs1204915217

Molecular consequence:

NM_000335.5:c.1890G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001099404.2:c.1890G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001099405.2:c.1890G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001160160.2:c.1890G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001160161.2:c.1890G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001354701.2:c.1890G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_198056.3:c.1890G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Functional consequence:

sequence_variant_affecting_splicing [Sequence Ontology: SO:1000071]

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
SCV000737544	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Apr 11, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20129283, 22885917 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000737544

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Apr 11, 2024)

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

The diagnostic and therapeutic aspects of loss-of-function cardiac sodium channelopathies in children.

Chockalingam P, Clur SA, Breur JM, Kriebel T, Paul T, Rammeloo LA, Wilde AA, Blom NA.

Heart Rhythm. 2012 Dec;9(12):1986-92. doi: 10.1016/j.hrthm.2012.08.011. Epub 2012 Aug 8.

PubMed [citation]

PMID:: 22885917

Details of each submission

From Ambry Genetics, SCV000737544.7

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

Description

The c.1890G>A (p.T630T) alteration is located in exon 12 (coding exon 11) of the SCN5A gene. This alteration consists of a G to A substitution at nucleotide position 1890. This nucleotide substitution does not change the threonine at codon 630. However, this change occurs in the last base pair of coding exon 11, which makes it likely to have some effect on normal mRNA splicing. Based on data from gnomAD, the A allele has an overall frequency of 0.001% (1/174574) total alleles studied. The highest observed frequency was 0.005% (1/21048) of Latino alleles. This variant was observed in individuals reported to have Brugada syndrome; however, clinical details were limited (Kapplinger, 2010; Chockalingam, 2012). This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Based on the available evidence, this alteration is classified as likely 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: Nov 10, 2024

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