NM_000335.5(SCN5A):c.5536C>G (p.Arg1846Gly) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 22, 2022
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:: RCV003656787.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.5536C>G (p.Arg1846Gly)]

NM_000335.5(SCN5A):c.5536C>G (p.Arg1846Gly)

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.5536C>G (p.Arg1846Gly)

HGVS:

NC_000003.12:g.38550833G>C
NG_008934.1:g.103840C>G
NM_000335.5:c.5536C>GMANE SELECT
NM_001099404.2:c.5539C>G
NM_001099405.2:c.5485C>G
NM_001160160.2:c.5440C>G
NM_001160161.2:c.5377C>G
NM_001354701.2:c.5482C>G
NM_198056.3:c.5539C>G
NP_000326.2:p.Arg1846Gly
NP_001092874.1:p.Arg1847Gly
NP_001092875.1:p.Arg1829Gly
NP_001153632.1:p.Arg1814Gly
NP_001153633.1:p.Arg1793Gly
NP_001341630.1:p.Arg1828Gly
NP_932173.1:p.Arg1847Gly
LRG_289t1:c.5539C>G
LRG_289:g.103840C>G
NC_000003.11:g.38592324G>C
NM_198056.2:c.5539C>G

Protein change:

R1793G

Links:

dbSNP: rs768246863

NCBI 1000 Genomes Browser:

rs768246863

Molecular consequence:

NM_000335.5:c.5536C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.5539C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.5485C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.5440C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.5377C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.5482C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.5539C>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001486004	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 22, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23321620, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001486004

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 22, 2022)

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

Genetics can contribute to the prognosis of Brugada syndrome: a pilot model for risk stratification.

Sommariva E, Pappone C, Martinelli Boneschi F, Di Resta C, Rosaria Carbone M, Salvi E, Vergara P, Sala S, Cusi D, Ferrari M, Benedetti S.

Eur J Hum Genet. 2013 Sep;21(9):911-7. doi: 10.1038/ejhg.2012.289. Epub 2013 Jan 16.

PubMed [citation]

PMID:: 23321620
PMCID:: PMC3746265

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, SCV001486004.3

#	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. This variant disrupts the p.Arg1847 amino acid residue in SCN5A. Other variant(s) that disrupt this residue have been observed in individuals with SCN5A-related conditions (PMID: 23321620), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 1000832). This missense change has been observed in individual(s) with clinical features of long QT syndrome (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1847 of the SCN5A protein (p.Arg1847Gly).

#	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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