NM_000335.5(SCN5A):c.43A>G (p.Arg15Gly) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 27, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001564789.12

Allele description

NM_000335.5(SCN5A):c.43A>G (p.Arg15Gly)

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.43A>G (p.Arg15Gly)

HGVS:

NC_000003.12:g.38633265T>C
NG_008934.1:g.21408A>G
NM_000335.5:c.43A>GMANE SELECT
NM_001099404.2:c.43A>G
NM_001099405.2:c.43A>G
NM_001160160.2:c.43A>G
NM_001160161.2:c.43A>G
NM_001354701.2:c.43A>G
NM_198056.3:c.43A>G
NP_000326.2:p.Arg15Gly
NP_001092874.1:p.Arg15Gly
NP_001092875.1:p.Arg15Gly
NP_001153632.1:p.Arg15Gly
NP_001153633.1:p.Arg15Gly
NP_001341630.1:p.Arg15Gly
NP_932173.1:p.Arg15Gly
LRG_289t1:c.43A>G
LRG_289:g.21408A>G
NC_000003.11:g.38674756T>C
NC_000003.11:g.38674756T>C
NM_198056.2:c.43A>G

Protein change:

R15G

Links:

dbSNP: rs752553088

NCBI 1000 Genomes Browser:

rs752553088

Molecular consequence:

NM_000335.5:c.43A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.43A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.43A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.43A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.43A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.43A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.43A>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
SCV001788004	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jun 12, 2020)	germline	clinical testing	Citation Link,
SCV003473798	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 27, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24631775, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001788004

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jun 12, 2020)

germline

clinical testing

Citation Link,

SCV003473798

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 27, 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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Cardiac channelopathy testing in 274 ethnically diverse sudden unexplained deaths.

Wang D, Shah KR, Um SY, Eng LS, Zhou B, Lin Y, Mitchell AA, Nicaj L, Prinz M, McDonald TV, Sampson BA, Tang Y.

Forensic Sci Int. 2014 Apr;237:90-9. doi: 10.1016/j.forsciint.2014.01.014. Epub 2014 Feb 15.

PubMed [citation]

PMID:: 24631775

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 GeneDx, SCV001788004.1

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29247119, 24631775)

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

From Invitae, SCV003473798.2

#	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. ClinVar contains an entry for this variant (Variation ID: 921391). This missense change has been observed in individual(s) with clinical features of SCN5A-related conditions (PMID: 24631775). This variant is present in population databases (rs752553088, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 15 of the SCN5A protein (p.Arg15Gly).

#	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: Sep 16, 2024

ClinVar

Relating variation to medicine