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NM_000335.5(SCN5A):c.5723A>G (p.Gln1908Arg) AND Cardiac arrhythmia

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Apr 3, 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:
RCV001842393.13

Allele description [Variation Report for NM_000335.5(SCN5A):c.5723A>G (p.Gln1908Arg)]

NM_000335.5(SCN5A):c.5723A>G (p.Gln1908Arg)

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.5723A>G (p.Gln1908Arg)
Other names:
p.Q1909R:CAG>CGG
HGVS:
  • NC_000003.12:g.38550646T>C
  • NG_008934.1:g.104027A>G
  • NM_000335.5:c.5723A>GMANE SELECT
  • NM_001099404.2:c.5726A>G
  • NM_001099405.2:c.5672A>G
  • NM_001160160.2:c.5627A>G
  • NM_001160161.2:c.5564A>G
  • NM_001354701.2:c.5669A>G
  • NM_198056.3:c.5726A>G
  • NP_000326.2:p.Gln1908Arg
  • NP_001092874.1:p.Gln1909Arg
  • NP_001092875.1:p.Gln1891Arg
  • NP_001153632.1:p.Gln1876Arg
  • NP_001153633.1:p.Gln1855Arg
  • NP_001341630.1:p.Gln1890Arg
  • NP_932173.1:p.Gln1909Arg
  • NP_932173.1:p.Gln1909Arg
  • LRG_289t1:c.5726A>G
  • LRG_289:g.104027A>G
  • LRG_289p1:p.Gln1909Arg
  • NC_000003.11:g.38592137T>C
  • NM_198056.2:c.5726A>G
  • Q14524:p.Gln1909Arg
Protein change:
Q1855R
Links:
UniProtKB: Q14524#VAR_068340; dbSNP: rs199473326
NCBI 1000 Genomes Browser:
rs199473326
Molecular consequence:
  • NM_000335.5:c.5723A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.5726A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.5672A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.5627A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.5564A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.5669A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.5726A>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
SCV001357588Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Mar 20, 2023) 		germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

SCV004816687All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Apr 3, 2023) 		germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided108544not providedclinical testing

Citations

PubMed

Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.

Tester DJ, Will ML, Haglund CM, Ackerman MJ.

Heart Rhythm. 2005 May;2(5):507-17.

PubMed [citation]
PMID:
15840476

Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants.

Kapa S, Tester DJ, Salisbury BA, Harris-Kerr C, Pungliya MS, Alders M, Wilde AA, Ackerman MJ.

Circulation. 2009 Nov 3;120(18):1752-60. doi: 10.1161/CIRCULATIONAHA.109.863076. Epub 2009 Oct 19.

PubMed [citation]
PMID:
19841300
PMCID:
PMC3025752
See all PubMed Citations (9)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001357588.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

This missense variant replaces glutamine with arginine at codon 1909 of the SCN5A protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Experimental electrophysiological studies using in vitro expression systems have shown this variant increases late sodium current (PMID: 25370050, 25757662, 25904541, 28087622, 28734073). However, clinical relevance of this observation is not clear. This variant has been reported in an individual affected with long QT syndrome (PMID: 19841300), in an individual affected with sudden infant death syndrome (PMID: 25757662), and in an individual referred for long QT syndrome genetic testing (PMID: 15840476). This variant has also been reported in an individual with normal QT interval (PMID: 26159999). 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, SCV004816687.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (9)

Description

This missense variant replaces glutamine with arginine at codon 1909 of the SCN5A protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Experimental electrophysiological studies using in vitro expression systems have shown this variant increases late sodium current (PMID: 25370050, 25757662, 25904541, 28087622, 28734073). However, clinical relevance of this observation is not clear. This variant has been reported in an individual affected with long QT syndrome (PMID: 19841300), in an individual affected with sudden infant death syndrome (PMID: 25757662), and in an individual referred for long QT syndrome genetic testing (PMID: 15840476). This variant has also been reported in an individual with normal QT interval (PMID: 26159999). 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: Oct 13, 2024