NM_006514.4(SCN10A):c.3151G>A (p.Gly1051Arg) AND Brugada syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 30, 2021
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:: RCV000462073.3

Allele description [Variation Report for NM_006514.4(SCN10A):c.3151G>A (p.Gly1051Arg)]

NM_006514.4(SCN10A):c.3151G>A (p.Gly1051Arg)

Genes:

LOC110121288:VISTA enhancer hs2268 [Gene]
SCN10A:sodium voltage-gated channel alpha subunit 10 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_006514.4(SCN10A):c.3151G>A (p.Gly1051Arg)

HGVS:

NC_000003.12:g.38725251C>T
NG_031891.2:g.73760G>A
NG_053903.1:g.3216C>T
NM_001293306.2:c.3148G>A
NM_001293307.2:c.2857G>A
NM_006514.2:c.3151G>A
NM_006514.4:c.3151G>AMANE SELECT
NP_001280235.2:p.Gly1050Arg
NP_001280236.2:p.Gly953Arg
NP_006505.3:p.Gly1051Arg
NP_006505.4:p.Gly1051Arg
NC_000003.11:g.38766742C>T
NM_006514.3:c.3151G>A

Protein change:

G1050R

Links:

dbSNP: rs374447261

NCBI 1000 Genomes Browser:

rs374447261

Molecular consequence:

NM_001293306.2:c.3148G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293307.2:c.2857G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006514.4:c.3151G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Brugada syndrome
Synonyms:: Sudden unexpected nocturnal death syndrome; Sudden unexplained nocturnal death syndrome; Sudden Unexplained Death Syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015263; MedGen: C1142166; OMIM: PS601144

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000547189	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 30, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000547189

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 30, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV000547189.3

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

Description

This sequence change replaces glycine with arginine at codon 1051 of the SCN10A protein (p.Gly1051Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs374447261, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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: Sep 29, 2024

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