NM_000335.5(SCN5A):c.1756G>A (p.Ala586Thr) AND Cardiac arrhythmia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 22, 2020
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:: RCV001842297.10

Allele description [Variation Report for NM_000335.5(SCN5A):c.1756G>A (p.Ala586Thr)]

NM_000335.5(SCN5A):c.1756G>A (p.Ala586Thr)

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.1756G>A (p.Ala586Thr)

HGVS:

NC_000003.12:g.38603846C>T
NG_008934.1:g.50827G>A
NM_000335.5:c.1756G>AMANE SELECT
NM_001099404.2:c.1756G>A
NM_001099405.2:c.1756G>A
NM_001160160.2:c.1756G>A
NM_001160161.2:c.1756G>A
NM_001354701.2:c.1756G>A
NM_198056.3:c.1756G>A
NP_000326.2:p.Ala586Thr
NP_001092874.1:p.Ala586Thr
NP_001092875.1:p.Ala586Thr
NP_001153632.1:p.Ala586Thr
NP_001153633.1:p.Ala586Thr
NP_001341630.1:p.Ala586Thr
NP_932173.1:p.Ala586Thr
NP_932173.1:p.Ala586Thr
LRG_289t1:c.1756G>A
LRG_289:g.50827G>A
LRG_289p1:p.Ala586Thr
NC_000003.11:g.38645337C>T
NM_198056.2:c.1756G>A

Protein change:

A586T

Links:

dbSNP: rs199473129

NCBI 1000 Genomes Browser:

rs199473129

Molecular consequence:

NM_000335.5:c.1756G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.1756G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.1756G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.1756G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.1756G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.1756G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.1756G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiac arrhythmia
Synonyms:: Cardiac rhythm disease
Identifiers:: EFO: EFO_0004269; MONDO: MONDO:0007263; MedGen: C0003811; Human Phenotype Ontology: HP:0011675

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PREDICTED: Fragaria vesca subsp. vesca caffeoylshikimate esterase (LOC105350276)...
PREDICTED: Fragaria vesca subsp. vesca caffeoylshikimate esterase (LOC105350276), mRNA
gi|764552337|ref|XM_011461957.1|

Nucleotide
nucleolar protein 16 isoform 1 [Homo sapiens]
nucleolar protein 16 isoform 1 [Homo sapiens]
gi|604723336|ref|NP_001243468.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001342758	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 22, 2020)	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

SCV001342758

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 22, 2020)

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001342758.2

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

Description

This missense variant replaces alanine with threonine at codon 586 of the SCN5A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in 1 individual affected with Brugada-pattern electrocardiogram (PMID: 21321465). This variant has been identified in 4/248302 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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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