NM_000335.5(SCN5A):c.5596G>T (p.Glu1866Ter) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 30, 2018
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:: RCV003540721.3

Allele description [Variation Report for NM_000335.5(SCN5A):c.5596G>T (p.Glu1866Ter)]

NM_000335.5(SCN5A):c.5596G>T (p.Glu1866Ter)

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.5596G>T (p.Glu1866Ter)

HGVS:

NC_000003.12:g.38550773C>A
NG_008934.1:g.103900G>T
NM_000335.5:c.5596G>TMANE SELECT
NM_001099404.2:c.5599G>T
NM_001099405.2:c.5545G>T
NM_001160160.2:c.5500G>T
NM_001160161.2:c.5437G>T
NM_001354701.2:c.5542G>T
NM_198056.3:c.5599G>T
NP_000326.2:p.Glu1866Ter
NP_001092874.1:p.Glu1867Ter
NP_001092875.1:p.Glu1849Ter
NP_001153632.1:p.Glu1834Ter
NP_001153633.1:p.Glu1813Ter
NP_001341630.1:p.Glu1848Ter
NP_932173.1:p.Glu1867Ter
NP_932173.1:p.Glu1867Ter
LRG_289t1:c.5599G>T
LRG_289:g.103900G>T
LRG_289p1:p.Glu1867Ter
NC_000003.11:g.38592264C>A
NM_198056.2:c.5599G>T

Protein change:

E1813*

Links:

dbSNP: rs1559720176

NCBI 1000 Genomes Browser:

rs1559720176

Molecular consequence:

NM_000335.5:c.5596G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001099404.2:c.5599G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001099405.2:c.5545G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001160160.2:c.5500G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001160161.2:c.5437G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354701.2:c.5542G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_198056.3:c.5599G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000822932	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Mar 30, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000822932

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Mar 30, 2018)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000822932.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change results in a premature translational stop signal in the SCN5A gene (p.Glu1867*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 150 amino acids of the SCN5A protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN5A-related disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Several missense variants located downstream of this variant (p.Gly1935Ser, p.Ala1949Pro, and p.Val2016Met) have been reported in individuals affected with Brugada syndrome (PMID:¬†16267250, 19406494,¬†24895455).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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