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NM_000335.5(SCN5A):c.5347G>A (p.Glu1783Lys) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 18, 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:
RCV000245905.5

Allele description [Variation Report for NM_000335.5(SCN5A):c.5347G>A (p.Glu1783Lys)]

NM_000335.5(SCN5A):c.5347G>A (p.Glu1783Lys)

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.5347G>A (p.Glu1783Lys)
Other names:
p.E1784K:GAG>AAG
HGVS:
  • NC_000003.12:g.38551022C>T
  • NG_008934.1:g.103651G>A
  • NM_000335.5:c.5347G>AMANE SELECT
  • NM_001099404.2:c.5350G>A
  • NM_001099405.2:c.5296G>A
  • NM_001160160.2:c.5251G>A
  • NM_001160161.2:c.5188G>A
  • NM_001354701.2:c.5293G>A
  • NM_198056.3:c.5350G>A
  • NP_000326.2:p.Glu1783Lys
  • NP_001092874.1:p.Glu1784Lys
  • NP_001092875.1:p.Glu1766Lys
  • NP_001153632.1:p.Glu1751Lys
  • NP_001153633.1:p.Glu1730Lys
  • NP_001341630.1:p.Glu1765Lys
  • NP_932173.1:p.Glu1784Lys
  • NP_932173.1:p.Glu1784Lys
  • LRG_289t1:c.5350G>A
  • LRG_289t3:c.5350G>A
  • LRG_289:g.103651G>A
  • LRG_289p1:p.Glu1784Lys
  • NC_000003.11:g.38592513C>T
  • NM_001099404.1:c.5350G>A
  • NM_001099404.2:c.5350G>A
  • NM_198056.2:c.5350G>A
  • Q14524:p.Glu1784Lys
Protein change:
E1730K; GLU1784LYS
Links:
UniProtKB: Q14524#VAR_008959; OMIM: 600163.0008; dbSNP: rs137854601
NCBI 1000 Genomes Browser:
rs137854601
Molecular consequence:
  • NM_000335.5:c.5347G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.5350G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.5296G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.5251G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.5188G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.5293G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.5350G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000319877Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jun 18, 2021) 		germlineclinical testing

PubMed (9)
[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

Catecholamine-provoked microvoltage T wave alternans in genotyped long QT syndrome.

Nemec J, Ackerman MJ, Tester DJ, Hejlik J, Shen WK.

Pacing Clin Electrophysiol. 2003 Aug;26(8):1660-7.

PubMed [citation]
PMID:
12877697

Gene sequencing in neonates and infants with the long QT syndrome.

Shim SH, Ito M, Maher T, Milunsky A.

Genet Test. 2005 Winter;9(4):281-4.

PubMed [citation]
PMID:
16379539
See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV000319877.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

The p.E1784K pathogenic mutation (also known as c.5350G>A), located in coding exon 27 of the SCN5A gene, results from a G to A substitution at nucleotide position 5350. The glutamic acid at codon 1784 is replaced by lysine, an amino acid with some similar properties. The first report of this mutation involved a family with a clinical diagnosis of autosomal dominant long QT syndrome (LQTS), in which the mutation was confirmed to co-segregrate in all affected, but none of the unaffected, family members. Functional analysis revealed a negative shift of steady-state sodium channel activation, thus suggesting delayed cardiac repolarization (Wei et al. Circulation. 1999:99(24):3165-71). Additional functional analysis revealed p.E1784K induced persistent inward sodium current activity with a faster recovery from the inactivation state suggesting an unstable inactivation state overall (Deschenes et al. Cardiovasc Res. 2000;46(1):55-65). There are reports of mixed clinical phenotypes involving LQTS, Brugada syndrome (BrS), and sinus node dysfunction among individuals with the p.E1784K mutation (Makita et al. J Clin Invest. 2008;118(6):2219-29; Sandhu A et al. Clin Case Rep 2017 Aug;5(8):1315-1319). This is considered the most common SCN5A mutation, and most recently demonstrated segregation in a family with BrS, LQTS, and cardiac conduction disease (CCD) (Veltmann C et al. J Am Heart Assoc. 2016;5(7):e003379). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Dec 7, 2024