NM_000335.5(SCN5A):c.5339A>G (p.Glu1780Gly) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 26, 2019
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:: RCV003541103.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.5339A>G (p.Glu1780Gly)]

NM_000335.5(SCN5A):c.5339A>G (p.Glu1780Gly)

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.5339A>G (p.Glu1780Gly)

HGVS:

NC_000003.12:g.38551030T>C
NG_008934.1:g.103643A>G
NM_000335.5:c.5339A>GMANE SELECT
NM_001099404.2:c.5342A>G
NM_001099405.2:c.5288A>G
NM_001160160.2:c.5243A>G
NM_001160161.2:c.5180A>G
NM_001354701.2:c.5285A>G
NM_198056.3:c.5342A>G
NP_000326.2:p.Glu1780Gly
NP_001092874.1:p.Glu1781Gly
NP_001092875.1:p.Glu1763Gly
NP_001153632.1:p.Glu1748Gly
NP_001153633.1:p.Glu1727Gly
NP_001341630.1:p.Glu1762Gly
NP_932173.1:p.Glu1781Gly
NP_932173.1:p.Glu1781Gly
LRG_289t1:c.5342A>G
LRG_289:g.103643A>G
LRG_289p1:p.Glu1781Gly
NC_000003.11:g.38592521T>C
NM_198056.2:c.5342A>G

Protein change:

E1727G

Links:

dbSNP: rs1217594631

NCBI 1000 Genomes Browser:

rs1217594631

Molecular consequence:

NM_000335.5:c.5339A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.5342A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.5288A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.5243A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.5180A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.5285A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.5342A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001201184	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 26, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23174487, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001201184

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 26, 2019)

germline

clinical testing

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

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

Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations.

Mullally J, Goldenberg I, Moss AJ, Lopes CM, Ackerman MJ, Zareba W, McNitt S, Robinson JL, Benhorin J, Kaufman ES, Towbin JA, Barsheshet A.

Heart Rhythm. 2013 Mar;10(3):378-82. doi: 10.1016/j.hrthm.2012.11.006. Epub 2012 Nov 19.

PubMed [citation]

PMID:: 23174487
PMCID:: PMC3690288

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, SCV001201184.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in an individual affected with long QT-syndrome (LQTS) (PMID: 23174487). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glycine at codon 1781 of the SCN5A protein (p.Glu1781Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine.

#	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: Oct 26, 2024

ClinVar

Relating variation to medicine