NM_006514.4(SCN10A):c.1516C>A (p.His506Asn) AND Brugada syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 1, 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:: RCV001050332.4

Allele description [Variation Report for NM_006514.4(SCN10A):c.1516C>A (p.His506Asn)]

NM_006514.4(SCN10A):c.1516C>A (p.His506Asn)

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.1516C>A (p.His506Asn)

HGVS:

NC_000003.12:g.38752458G>T
NG_031891.2:g.46553C>A
NM_001293306.2:c.1516C>A
NM_001293307.2:c.1462-2274C>A
NM_006514.4:c.1516C>AMANE SELECT
NP_001280235.2:p.His506Asn
NP_006505.3:p.His506Asn
NP_006505.4:p.His506Asn
NC_000003.11:g.38793949G>T
NM_006514.2:c.1516C>A
NM_006514.3:c.1516C>A

Protein change:

H506N

Links:

dbSNP: rs745555704

NCBI 1000 Genomes Browser:

rs745555704

Molecular consequence:

NM_001293307.2:c.1462-2274C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001293306.2:c.1516C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006514.4:c.1516C>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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ART4 [Hylobates moloch]
ART4 [Hylobates moloch]
Gene ID:116472722

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LCT [Moschus berezovskii]
LCT [Moschus berezovskii]
Gene ID:129537793

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001214431	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25053638, 28407228, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001214431

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2021)

germline

clinical testing

PubMed (3)
[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

SCN10A/Nav1.8 modulation of peak and late sodium currents in patients with early onset atrial fibrillation.

Savio-Galimberti E, Weeke P, Muhammad R, Blair M, Ansari S, Short L, Atack TC, Kor K, Vanoye CG, Olesen MS, LuCamp, Yang T, George AL Jr, Roden DM, Darbar D.

Cardiovasc Res. 2014 Nov 1;104(2):355-63. doi: 10.1093/cvr/cvu170. Epub 2014 Jul 22.

PubMed [citation]

PMID:: 25053638
PMCID:: PMC4271018

Deleterious protein-altering mutations in the SCN10A voltage-gated sodium channel gene are associated with prolonged QT.

Abou Ziki MD, Seidelmann SB, Smith E, Atteya G, Jiang Y, Fernandes RG, Marieb MA, Akar JG, Mani A.

Clin Genet. 2018 Apr;93(4):741-751. doi: 10.1111/cge.13036. Epub 2017 May 18.

PubMed [citation]

PMID:: 28407228
PMCID:: PMC5640462

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001214431.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces histidine with asparagine at codon 506 of the SCN10A protein (p.His506Asn). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and asparagine. This variant is present in population databases (rs745555704, ExAC 0.002%). This missense change has been observed in individual(s) with paroxysmal atrial fibrillation (PMID: 25053638, 28407228). 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 tolerated. 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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