NM_000335.5(SCN5A):c.1333C>G (p.His445Asp) AND Brugada syndrome

Clinical significance:Uncertain significance (Last evaluated: Sep 8, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000458775.5

Allele description [Variation Report for NM_000335.5(SCN5A):c.1333C>G (p.His445Asp)]

NM_000335.5(SCN5A):c.1333C>G (p.His445Asp)

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.1333C>G (p.His445Asp)
HGVS:
  • NC_000003.12:g.38605956G>C
  • NG_008934.1:g.48717C>G
  • NM_000335.5:c.1333C>GMANE SELECT
  • NM_001099404.2:c.1333C>G
  • NM_001099405.2:c.1333C>G
  • NM_001160160.2:c.1333C>G
  • NM_001160161.2:c.1333C>G
  • NM_001354701.2:c.1333C>G
  • NM_198056.2:c.1333C>G
  • NM_198056.3:c.1333C>G
  • NP_000326.2:p.His445Asp
  • NP_001092874.1:p.His445Asp
  • NP_001092875.1:p.His445Asp
  • NP_001153632.1:p.His445Asp
  • NP_001153633.1:p.His445Asp
  • NP_001341630.1:p.His445Asp
  • NP_932173.1:p.His445Asp
  • NP_932173.1:p.His445Asp
  • LRG_289t1:c.1333C>G
  • LRG_289:g.48717C>G
  • LRG_289p1:p.His445Asp
  • NC_000003.11:g.38647447G>C
  • Q14524:p.His445Asp
Protein change:
H445D; HIS445ASP
Links:
UniProtKB: Q14524#VAR_055173; OMIM: 600163.0042; dbSNP: rs199473112
NCBI 1000 Genomes Browser:
rs199473112
Molecular consequence:
  • NM_000335.5:c.1333C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.1333C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.1333C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.1333C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.1333C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.1333C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.2:c.1333C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.1333C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Brugada syndrome
Synonyms:
Sudden unexpected nocturnal death syndrome; Sudden unexplained nocturnal death syndrome; Sudden Unexplained Death Syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015263; MedGen: C1142166; OMIM: PS601144

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000545010Invitaecriteria provided, single submitter
Uncertain significance
(Sep 8, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Testing the burden of rare variation in arrhythmia-susceptibility genes provides new insights into molecular diagnosis for Brugada syndrome.

Le Scouarnec S, Karakachoff M, Gourraud JB, Lindenbaum P, Bonnaud S, Portero V, Duboscq-Bidot L, Daumy X, Simonet F, Teusan R, Baron E, Violleau J, Persyn E, Bellanger L, Barc J, Chatel S, Martins R, Mabo P, Sacher F, Haïssaguerre M, Kyndt F, Schmitt S, et al.

Hum Mol Genet. 2015 May 15;24(10):2757-63. doi: 10.1093/hmg/ddv036. Epub 2015 Feb 3.

PubMed [citation]
PMID:
25650408

Clinical presentation and follow-up of women affected by Brugada syndrome.

Berthome P, Tixier R, Briand J, Geoffroy O, Babuty D, Mansourati J, Jesel L, Dupuis JM, Bru P, Kyndt F, Guyomarch B, Thollet A, Behar N, Mabo P, Sacher F, Probst V, Gourraud JB.

Heart Rhythm. 2019 Feb;16(2):260-267. doi: 10.1016/j.hrthm.2018.08.032. Epub 2018 Sep 5.

PubMed [citation]
PMID:
30193851
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000545010.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces histidine with aspartic acid at codon 445 of the SCN5A protein (p.His445Asp). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and aspartic acid. This variant is present in population databases (rs199473112, ExAC 0.02%). This variant has been reported in individuals affected with Brugada syndrome and lone atrial fibrillation (PMID: 25650408, 30193851, 19808477). It was also shown to segregate with disease in a family affected with atrial fibrillation (PMID: 18378609). ClinVar contains an entry for this variant (Variation ID: 30046). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C2). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 5

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

Last Updated: Nov 27, 2021

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