NM_000335.5(SCN5A):c.784A>G (p.Ser262Gly) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 14, 2023
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:: RCV003539998.3

Allele description [Variation Report for NM_000335.5(SCN5A):c.784A>G (p.Ser262Gly)]

NM_000335.5(SCN5A):c.784A>G (p.Ser262Gly)

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.784A>G (p.Ser262Gly)

HGVS:

NC_000003.12:g.38609884T>C
NG_008934.1:g.44789A>G
NM_000335.5:c.784A>GMANE SELECT
NM_001099404.2:c.784A>G
NM_001099405.2:c.784A>G
NM_001160160.2:c.784A>G
NM_001160161.2:c.784A>G
NM_001354701.2:c.784A>G
NM_198056.3:c.784A>G
NP_000326.2:p.Ser262Gly
NP_001092874.1:p.Ser262Gly
NP_001092875.1:p.Ser262Gly
NP_001153632.1:p.Ser262Gly
NP_001153633.1:p.Ser262Gly
NP_001341630.1:p.Ser262Gly
NP_932173.1:p.Ser262Gly
NP_932173.1:p.Ser262Gly
LRG_289t1:c.784A>G
LRG_289:g.44789A>G
LRG_289p1:p.Ser262Gly
NC_000003.11:g.38651375T>C
NM_198056.2:c.784A>G

Protein change:

S262G

Links:

dbSNP: rs777689378

NCBI 1000 Genomes Browser:

rs777689378

Molecular consequence:

NM_000335.5:c.784A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.784A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.784A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.784A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.784A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.784A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.784A>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
SCV000760254	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 14, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27287068, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000760254

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 14, 2023)

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

Electrophysiological characterization of a large set of novel variants in the SCN5A-gene: identification of novel LQTS3 and BrS mutations.

Ortiz-Bonnin B, Rinné S, Moss R, Streit AK, Scharf M, Richter K, Stöber A, Pfeufer A, Seemann G, Kääb S, Beckmann BM, Decher N.

Pflugers Arch. 2016 Aug;468(8):1375-87. doi: 10.1007/s00424-016-1844-3. Epub 2016 Jun 11.

PubMed [citation]

PMID:: 27287068

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, SCV000760254.3

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

Description

This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 262 of the SCN5A protein (p.Ser262Gly). This variant is present in population databases (rs777689378, gnomAD 0.007%). This missense change has been observed in individual(s) with dilated cardiomyopathy and/or long QT syndrome (PMID: 27287068; Invitae). ClinVar contains an entry for this variant (Variation ID: 532103). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. Experimental studies have shown that this missense change does not substantially affect SCN5A function (PMID: 27287068). 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: Nov 10, 2024

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