NM_000335.5(SCN5A):c.5479G>A (p.Ala1827Thr) AND Brugada syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 26, 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:: RCV000477269.13

Allele description [Variation Report for NM_000335.5(SCN5A):c.5479G>A (p.Ala1827Thr)]

NM_000335.5(SCN5A):c.5479G>A (p.Ala1827Thr)

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.5479G>A (p.Ala1827Thr)

Other names:

p.A1828T:GCC>ACC

HGVS:

NC_000003.12:g.38550890C>T
NG_008934.1:g.103783G>A
NM_000335.5:c.5479G>AMANE SELECT
NM_001099404.2:c.5482G>A
NM_001099405.2:c.5428G>A
NM_001160160.2:c.5383G>A
NM_001160161.2:c.5320G>A
NM_001354701.2:c.5425G>A
NM_198056.3:c.5482G>A
NP_000326.2:p.Ala1827Thr
NP_001092874.1:p.Ala1828Thr
NP_001092875.1:p.Ala1810Thr
NP_001153632.1:p.Ala1795Thr
NP_001153633.1:p.Ala1774Thr
NP_001341630.1:p.Ala1809Thr
NP_932173.1:p.Ala1828Thr
NP_932173.1:p.Ala1828Thr
LRG_289t1:c.5482G>A
LRG_289:g.103783G>A
LRG_289p1:p.Ala1828Thr
NC_000003.11:g.38592381C>T
NM_001099404.1:c.5482G>A
NM_198056.2:c.5482G>A

Protein change:

A1774T

Links:

dbSNP: rs774593360

NCBI 1000 Genomes Browser:

rs774593360

Molecular consequence:

NM_000335.5:c.5479G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.5482G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.5428G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.5383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.5320G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.5425G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.5482G>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
SCV000545038	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 26, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31983221, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000545038

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 26, 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Reevaluating the Genetic Contribution of Monogenic Dilated Cardiomyopathy.

Mazzarotto F, Tayal U, Buchan RJ, Midwinter W, Wilk A, Whiffin N, Govind R, Mazaika E, de Marvao A, Dawes TJW, Felkin LE, Ahmad M, Theotokis PI, Edwards E, Ing AY, Thomson KL, Chan LLH, Sim D, Baksi AJ, Pantazis A, Roberts AM, Watkins H, et al.

Circulation. 2020 Feb 4;141(5):387-398. doi: 10.1161/CIRCULATIONAHA.119.037661. Epub 2020 Jan 27.

PubMed [citation]

PMID:: 31983221
PMCID:: PMC7004454

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, SCV000545038.5

#	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 alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1828 of the SCN5A protein (p.Ala1828Thr). This variant is present in population databases (rs774593360, gnomAD 0.01%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 31983221). ClinVar contains an entry for this variant (Variation ID: 201539). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 8, 2024

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