NM_000335.5(SCN5A):c.5753G>A (p.Arg1918His) AND Cardiac arrhythmia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 10, 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:: RCV001842721.11

Allele description [Variation Report for NM_000335.5(SCN5A):c.5753G>A (p.Arg1918His)]

NM_000335.5(SCN5A):c.5753G>A (p.Arg1918His)

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.5753G>A (p.Arg1918His)

HGVS:

NC_000003.12:g.38550616C>T
NG_008934.1:g.104057G>A
NM_000335.5:c.5753G>AMANE SELECT
NM_001099404.2:c.5756G>A
NM_001099405.2:c.5702G>A
NM_001160160.2:c.5657G>A
NM_001160161.2:c.5594G>A
NM_001354701.2:c.5699G>A
NM_198056.3:c.5756G>A
NP_000326.2:p.Arg1918His
NP_001092874.1:p.Arg1919His
NP_001092875.1:p.Arg1901His
NP_001153632.1:p.Arg1886His
NP_001153633.1:p.Arg1865His
NP_001341630.1:p.Arg1900His
NP_932173.1:p.Arg1919His
LRG_289t1:c.5756G>A
LRG_289:g.104057G>A
NC_000003.11:g.38592107C>T
NC_000003.11:g.38592107C>T
NM_198056.2:c.5756G>A

Protein change:

R1865H

Links:

dbSNP: rs141107387

NCBI 1000 Genomes Browser:

rs141107387

Molecular consequence:

NM_000335.5:c.5753G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.5756G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.5702G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.5657G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.5594G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.5699G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.5756G>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001342620	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 10, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28341781, 34814702, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001342620

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 10, 2023)

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

Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry.

Yamagata K, Horie M, Aiba T, Ogawa S, Aizawa Y, Ohe T, Yamagishi M, Makita N, Sakurada H, Tanaka T, Shimizu A, Hagiwara N, Kishi R, Nakano Y, Takagi M, Makiyama T, Ohno S, Fukuda K, Watanabe H, Morita H, Hayashi K, Kusano K, et al.

Circulation. 2017 Jun 6;135(23):2255-2270. doi: 10.1161/CIRCULATIONAHA.117.027983. Epub 2017 Mar 24.

PubMed [citation]

PMID:: 28341781

Prevalence of Inherited Cardiac Diseases Among Young Patients Requiring Permanent Pacing.

Tassetti L, Girolami F, Fumagalli C, Argirò A, Ricciardi G, Checchi L, Zocchi C, Berteotti M, Tomberli B, Gabrielli E, Favilli S, Pieroni M, Cappelli F, Tanini I, Pieragnoli P, Marchionni N, Olivotto I.

Circ Arrhythm Electrophysiol. 2021 Dec;14(12):e010562. doi: 10.1161/CIRCEP.121.010562. Epub 2021 Nov 24. No abstract available.

PubMed [citation]

PMID:: 34814702

See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001342620.3

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

Description

This missense variant replaces arginine with histidine at codon 1919 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with Brugada syndrome (PMID: 28341781) and in an individual suspected of having inherited heart disease (PMID: 34814702). This variant has been identified in 2/249262 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: Oct 26, 2024

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