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NM_000335.5(SCN5A):c.4770G>A (p.Trp1590Ter) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 12, 2022
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:
RCV003542449.1

Allele description [Variation Report for NM_000335.5(SCN5A):c.4770G>A (p.Trp1590Ter)]

NM_000335.5(SCN5A):c.4770G>A (p.Trp1590Ter)

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.4770G>A (p.Trp1590Ter)
HGVS:
  • NC_000003.12:g.38554319C>T
  • NG_008934.1:g.100354G>A
  • NM_000335.5:c.4770G>AMANE SELECT
  • NM_001099404.2:c.4773G>A
  • NM_001099405.2:c.4719G>A
  • NM_001160160.2:c.4714+56G>A
  • NM_001160161.2:c.4611G>A
  • NM_001354701.2:c.4716G>A
  • NM_198056.3:c.4773G>A
  • NP_000326.2:p.Trp1590Ter
  • NP_000326.2:p.Trp1590Ter
  • NP_001092874.1:p.Trp1591Ter
  • NP_001092874.1:p.Trp1591Ter
  • NP_001092875.1:p.Trp1573Ter
  • NP_001153633.1:p.Trp1537Ter
  • NP_001341630.1:p.Trp1572Ter
  • NP_932173.1:p.Trp1591Ter
  • NP_932173.1:p.Trp1591Ter
  • LRG_289t1:c.4773G>A
  • LRG_289t2:c.4770G>A
  • LRG_289t3:c.4773G>A
  • LRG_289:g.100354G>A
  • LRG_289p1:p.Trp1591Ter
  • LRG_289p2:p.Trp1590Ter
  • LRG_289p3:p.Trp1591Ter
  • NC_000003.11:g.38595810C>T
  • NM_000335.4:c.4770G>A
  • NM_001099404.1:c.4773G>A
  • NM_198056.2:c.4773G>A
  • NR_176299.1:n.5519G>A
Protein change:
W1537*
Molecular consequence:
  • NM_001160160.2:c.4714+56G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000335.5:c.4770G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001099404.2:c.4773G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001099405.2:c.4719G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001160161.2:c.4611G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354701.2:c.4716G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_198056.3:c.4773G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003525140Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Apr 12, 2022) 		germlineclinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV003525140.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Trp1591*) in the SCN5A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 426 amino acid(s) of the SCN5A protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Brugada syndrome (PMID: 20129283). This variant disrupts a region of the SCN5A protein in which other variant(s) (p.Glu1867*) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Apr 20, 2024