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NM_000335.5(SCN5A):c.127C>T (p.Arg43Ter) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 2, 2021
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:
RCV002265957.8

Allele description [Variation Report for NM_000335.5(SCN5A):c.127C>T (p.Arg43Ter)]

NM_000335.5(SCN5A):c.127C>T (p.Arg43Ter)

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.127C>T (p.Arg43Ter)
HGVS:
  • NC_000003.12:g.38633181G>A
  • NG_008934.1:g.21492C>T
  • NM_000335.5:c.127C>TMANE SELECT
  • NM_001099404.2:c.127C>T
  • NM_001099405.2:c.127C>T
  • NM_001160160.2:c.127C>T
  • NM_001160161.2:c.127C>T
  • NM_001354701.2:c.127C>T
  • NM_198056.3:c.127C>T
  • NP_000326.2:p.Arg43Ter
  • NP_001092874.1:p.Arg43Ter
  • NP_001092875.1:p.Arg43Ter
  • NP_001153632.1:p.Arg43Ter
  • NP_001153633.1:p.Arg43Ter
  • NP_001341630.1:p.Arg43Ter
  • NP_932173.1:p.Arg43Ter
  • LRG_289t1:c.127C>T
  • LRG_289:g.21492C>T
  • NC_000003.11:g.38674672G>A
  • NM_198056.2:c.127C>T
Protein change:
R43*
Links:
dbSNP: rs1553607597
NCBI 1000 Genomes Browser:
rs1553607597
Molecular consequence:
  • NM_000335.5:c.127C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001099404.2:c.127C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001099405.2:c.127C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001160160.2:c.127C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001160161.2:c.127C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354701.2:c.127C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_198056.3:c.127C>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

Condition(s)

Name:
Brugada syndrome 1 (BRGDA1)
Synonyms:
Right bundle branch block, ST segment elevation, and sudden death syndrome
Identifiers:
MONDO: MONDO:0011001; MedGen: C4551804; Orphanet: 130; OMIM: 601144
Name:
Long QT syndrome 3 (LQT3)
Identifiers:
MONDO: MONDO:0011377; MedGen: C1859062; Orphanet: 101016; Orphanet: 768; OMIM: 603830

Recent activity

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002548570New York Genome Center - CSER-NYCKidSeq
criteria provided, single submitter

(NYGC Assertion Criteria 2020)		Pathogenic
(Jul 2, 2021) 		inheritedclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedinheritedunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Spectrum and prevalence of mutations involving BrS1- through BrS12-susceptibility genes in a cohort of unrelated patients referred for Brugada syndrome genetic testing: implications for genetic testing.

Crotti L, Marcou CA, Tester DJ, Castelletti S, Giudicessi JR, Torchio M, Medeiros-Domingo A, Simone S, Will ML, Dagradi F, Schwartz PJ, Ackerman MJ.

J Am Coll Cardiol. 2012 Oct 9;60(15):1410-8. doi: 10.1016/j.jacc.2012.04.037. Epub 2012 Jul 25.

PubMed [citation]
PMID:
22840528
PMCID:
PMC3624764

Details of each submission

From New York Genome Center - CSER-NYCKidSeq, SCV002548570.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The heterozygous nonsense variant c.127C>T, p.Arg43Ter in exon 2 of the SCN5A gene, creates a premature translation stop signal at AA 43. This variant isexpected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with Brugada syndrome (PMID:22840528). The variant is absent in the gnomAD v3.1.1 database, suggesting it is not a common benign variant in the populations represented in this database. Loss of function is a known mechanism of SCN5A associated Brugada syndrome. Based on available evidence, this variant is classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedunknown1not providednot provided1not providednot providednot provided

Last Updated: Oct 26, 2024