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

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 29, 2019
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:
RCV001841492.9

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:
Cardiac arrhythmia
Synonyms:
Cardiac rhythm disease
Identifiers:
EFO: EFO_0004269; MONDO: MONDO:0007263; MedGen: C0003811; Human Phenotype Ontology: HP:0011675

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001361002Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely pathogenic
(Oct 29, 2019) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001361002.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: SCN5A c.1890G>A (p.Thr630Thr) alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: One predicts that the variant abolishes a 5' splicing donor site, while four predict that the variant weakens a 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 5.7e-06 in 174574 control chromosomes (gnomAD). c.1890G>A has been reported in the literature in individuals affected with Arrhythmia [e.g. Kapplinger_2010 (Brugada Syndrome), Chockalingham_2012, Baruteau_2018]. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submissions (evaluation after 2014) cites the variant once as likely pathogenic and once as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 10, 2024