NM_000335.5(SCN5A):c.1705C>G (p.Arg569Gly) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 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:: RCV002408802.9

Allele description [Variation Report for NM_000335.5(SCN5A):c.1705C>G (p.Arg569Gly)]

NM_000335.5(SCN5A):c.1705C>G (p.Arg569Gly)

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.1705C>G (p.Arg569Gly)

Other names:

p.R569G:CGG>GGG

HGVS:

NC_000003.12:g.38603897G>C
NG_008934.1:g.50776C>G
NM_000335.5:c.1705C>GMANE SELECT
NM_001099404.2:c.1705C>G
NM_001099405.2:c.1705C>G
NM_001160160.2:c.1705C>G
NM_001160161.2:c.1705C>G
NM_001354701.2:c.1705C>G
NM_198056.3:c.1705C>G
NP_000326.2:p.Arg569Gly
NP_001092874.1:p.Arg569Gly
NP_001092875.1:p.Arg569Gly
NP_001092875.1:p.Arg569Gly
NP_001153632.1:p.Arg569Gly
NP_001153633.1:p.Arg569Gly
NP_001341630.1:p.Arg569Gly
NP_932173.1:p.Arg569Gly
NP_932173.1:p.Arg569Gly
LRG_289t1:c.1705C>G
LRG_289:g.50776C>G
LRG_289p1:p.Arg569Gly
NC_000003.11:g.38645388G>C
NM_001099405.1:c.1705C>G
NM_198056.2:c.1705C>G

Protein change:

R569G

Links:

dbSNP: rs199473576

NCBI 1000 Genomes Browser:

rs199473576

Molecular consequence:

NM_000335.5:c.1705C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.1705C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.1705C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.1705C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.1705C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.1705C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.1705C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002715806	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 1, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25904541, 32233023 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002715806

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 1, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Enhanced Classification of Brugada Syndrome-Associated and Long-QT Syndrome-Associated Genetic Variants in the SCN5A-Encoded Na(v)1.5 Cardiac Sodium Channel.

Kapplinger JD, Giudicessi JR, Ye D, Tester DJ, Callis TE, Valdivia CR, Makielski JC, Wilde AA, Ackerman MJ.

Circ Cardiovasc Genet. 2015 Aug;8(4):582-95. doi: 10.1161/CIRCGENETICS.114.000831. Epub 2015 Apr 22.

PubMed [citation]

PMID:: 25904541
PMCID:: PMC4878676

Wolff-Parkinson-White syndrome: De novo variants and evidence for mutational burden in genes associated with atrial fibrillation.

Coban-Akdemir ZH, Charng WL, Azamian M, Paine IS, Punetha J, Grochowski CM, Gambin T, Valdes SO, Cannon B, Zapata G, Hernandez PP, Jhangiani S, Doddapaneni H, Hu J, Boricha F, Muzny DM, Boerwinkle E, Yang Y, Gibbs RA, Posey JE, Wehrens XHT, Belmont JW, et al.

Am J Med Genet A. 2020 Jun;182(6):1387-1399. doi: 10.1002/ajmg.a.61571. Epub 2020 Mar 31.

PubMed [citation]

PMID:: 32233023
PMCID:: PMC7275694

Details of each submission

From Ambry Genetics, SCV002715806.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.R569G variant (also known as c.1705C>G), located in coding exon 11 of the SCN5A gene, results from a C to G substitution at nucleotide position 1705. The arginine at codon 569 is replaced by glycine, an amino acid with dissimilar properties. This alteration has been reported in a Wolf-Parkinson-White cohort; however, clinical details were limited (Coban-Akdemir ZH et al. Am J Med Genet A, 2020 06;182:1387-1399). Additionally, in vitro studies demonstrated that this alteration may have a deleterious effect on protein function (Kapplinger JD et al. Circ Cardiovasc Genet, 2015 Aug;8:582-95). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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