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NM_000335.5(SCN5A):c.210T>G (p.Asn70Lys) AND Cardiac arrhythmia

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Dec 13, 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:
RCV001842312.13

Allele description [Variation Report for NM_000335.5(SCN5A):c.210T>G (p.Asn70Lys)]

NM_000335.5(SCN5A):c.210T>G (p.Asn70Lys)

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.210T>G (p.Asn70Lys)
HGVS:
  • NC_000003.12:g.38633098A>C
  • NG_008934.1:g.21575T>G
  • NM_000335.5:c.210T>GMANE SELECT
  • NM_001099404.2:c.210T>G
  • NM_001099405.2:c.210T>G
  • NM_001160160.2:c.210T>G
  • NM_001160161.2:c.210T>G
  • NM_001354701.2:c.210T>G
  • NM_198056.3:c.210T>G
  • NP_000326.2:p.Asn70Lys
  • NP_001092874.1:p.Asn70Lys
  • NP_001092875.1:p.Asn70Lys
  • NP_001153632.1:p.Asn70Lys
  • NP_001153633.1:p.Asn70Lys
  • NP_001341630.1:p.Asn70Lys
  • NP_932173.1:p.Asn70Lys
  • NP_932173.1:p.Asn70Lys
  • LRG_289t1:c.210T>G
  • LRG_289:g.21575T>G
  • LRG_289p1:p.Asn70Lys
  • NC_000003.11:g.38674589A>C
  • NM_001099404.1:c.210T>G
  • NM_198056.2:c.210T>G
  • Q14524:p.Asn70Lys
Protein change:
N70K
Links:
UniProtKB: Q14524#VAR_074314; dbSNP: rs199473050
NCBI 1000 Genomes Browser:
rs199473050
Molecular consequence:
  • NM_000335.5:c.210T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.210T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.210T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.210T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.210T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.210T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.210T>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
8

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
SCV001360102Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Mar 2, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004818781All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Dec 13, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown8not providednot provided108544not providedclinical testing

Citations

PubMed

An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing.

Kapplinger JD, Tester DJ, Alders M, Benito B, Berthet M, Brugada J, Brugada P, Fressart V, Guerchicoff A, Harris-Kerr C, Kamakura S, Kyndt F, Koopmann TT, Miyamoto Y, Pfeiffer R, Pollevick GD, Probst V, Zumhagen S, Vatta M, Towbin JA, Shimizu W, Schulze-Bahr E, et al.

Heart Rhythm. 2010 Jan;7(1):33-46. doi: 10.1016/j.hrthm.2009.09.069. Epub 2009 Oct 8.

PubMed [citation]
PMID:
20129283
PMCID:
PMC2822446

Brugada syndrome disease phenotype explained in apparently benign sodium channel mutations.

Hoshi M, Du XX, Shinlapawittayatorn K, Liu H, Chai S, Wan X, Ficker E, Deschênes I.

Circ Cardiovasc Genet. 2014 Apr;7(2):123-31. doi: 10.1161/CIRCGENETICS.113.000292. Epub 2014 Feb 26.

PubMed [citation]
PMID:
24573164
PMCID:
PMC3989843
See all PubMed Citations (4)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001360102.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This missense variant replaces asparagine with lysine at codon 70 of the SCN5A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). A functional study has shown that this variant causes a reduction in sodium current density upon co-expression with wild type allele in HEK293 cells (PMID: 24573164). This variant has been reported in an individual suspected of having Brugada syndrome (PMID: 20129283) and in an individual with unspecified arrhythmia (PMID: 30847666). This variant has been identified in 11/247524 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.

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

From All of Us Research Program, National Institutes of Health, SCV004818781.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided8not providednot providedclinical testing PubMed (4)

Description

This missense variant replaces asparagine with lysine at codon 70 of the SCN5A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). A functional study has shown that this variant causes a reduction in sodium current density upon co-expression with wild type allele in HEK293 cells (PMID: 24573164). This variant has been reported in an individual suspected of having Brugada syndrome (PMID: 20129283) and in an individual with unspecified arrhythmia (PMID: 30847666). This variant has been identified in 11/247524 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided8not providednot providednot provided

Last Updated: Nov 3, 2024