NM_000335.5(SCN5A):c.1198G>A (p.Gly400Arg) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 19, 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:: RCV003541337.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.1198G>A (p.Gly400Arg)]

NM_000335.5(SCN5A):c.1198G>A (p.Gly400Arg)

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.1198G>A (p.Gly400Arg)

HGVS:

NC_000003.12:g.38606091C>T
NG_008934.1:g.48582G>A
NM_000335.5:c.1198G>AMANE SELECT
NM_001099404.2:c.1198G>A
NM_001099405.2:c.1198G>A
NM_001160160.2:c.1198G>A
NM_001160161.2:c.1198G>A
NM_001354701.2:c.1198G>A
NM_198056.3:c.1198G>A
NP_000326.2:p.Gly400Arg
NP_001092874.1:p.Gly400Arg
NP_001092875.1:p.Gly400Arg
NP_001153632.1:p.Gly400Arg
NP_001153633.1:p.Gly400Arg
NP_001341630.1:p.Gly400Arg
NP_932173.1:p.Gly400Arg
LRG_289:g.48582G>A
NC_000003.11:g.38647582C>T

Protein change:

G400R

Links:

dbSNP: rs2062008854

NCBI 1000 Genomes Browser:

rs2062008854

Molecular consequence:

NM_000335.5:c.1198G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.1198G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.1198G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.1198G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.1198G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.1198G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.1198G>A - 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
SCV001507110	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 19, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27707468, 28146213, 34048814, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001507110

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 19, 2022)

germline

clinical testing

PubMed (4)
[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

Does Sudden Unexplained Nocturnal Death Syndrome Remain the Autopsy-Negative Disorder: A Gross, Microscopic, and Molecular Autopsy Investigation in Southern China.

Zhang L, Tester DJ, Lang D, Chen Y, Zheng J, Gao R, Corliss RF, Tang S, Kyle JW, Liu C, Ackerman MJ, Makielski JC, Cheng J.

Mayo Clin Proc. 2016 Nov;91(11):1503-1514. doi: 10.1016/j.mayocp.2016.06.031. Epub 2016 Oct 1.

PubMed [citation]

PMID:: 27707468
PMCID:: PMC5097692

Compound Heterozygous SCN5A Mutations in a Toddler - Are they Associated with a More Severe Phenotype?

Sacilotto L, Epifanio HB, Darrieux FC, Wulkan F, Oliveira TG, Hachul DT, Pereira AD, Scanavacca MI.

Arq Bras Cardiol. 2017 Jan;108(1):70-73. doi: 10.5935/abc.20170006. Portuguese, English.

PubMed [citation]

PMID:: 28146213
PMCID:: PMC5245850

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001507110.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 400 of the SCN5A protein (p.Gly400Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Brugada syndrome (PMID: 27707468, 28146213). ClinVar contains an entry for this variant (Variation ID: 1017347). 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. Experimental studies have shown that this missense change affects SCN5A function (PMID: 34048814). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.

#	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 13, 2024

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