NM_000335.5(SCN5A):c.1890G>A (p.Thr630=) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 4, 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:: RCV003541209.1

Allele description

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)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001574354	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 4, 2024)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 20129283, 22885917, 30193851, 33221895, 17576681, 9536098, 36197721, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001574354

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 4, 2024)

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

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

See all PubMed Citations (8)

Details of each submission

From Invitae, SCV001574354.3

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

Description

This sequence change affects codon 630 of the SCN5A mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SCN5A protein. This variant also falls at the last nucleotide of exon 12, which is part of the consensus splice site for this exon. This variant is present in population databases (no rsID available, gnomAD 0.005%). This variant has been observed in individual(s) with clinical features of SCN5A-related conditions (PMID: 20129283, 22885917, 30193851, 33221895). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 505275). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 36197721). 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: Sep 16, 2024

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