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

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Oct 6, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001842935.13

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]
Observations:
1

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001348371Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Sep 21, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004837504All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Oct 6, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided108544not providedclinical 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
See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001348371.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This missense variant replaces arginine with glycine at codon 569 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). A functional study has reported that this variant together with p.Gln1077del affects sodium channel function (PMID: 25904541). This variant has been reported in an individual affected with Wolff-Parkinson-White syndrome (PMID: 32233023). This variant has not been identified 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From All of Us Research Program, National Institutes of Health, SCV004837504.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)

Description

This missense variant replaces arginine with glycine at codon 569 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). A functional study has reported that this variant together with p.Gln1077del affects sodium channel function (PMID: 25904541). This variant has been reported in an individual affected with Wolff-Parkinson-White syndrome (PMID: 32233023). This variant has not been identified 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided1not providednot providednot provided

Last Updated: Nov 10, 2024