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NM_000335.5(SCN5A):c.210T>G (p.Asn70Lys) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 15, 2022
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:
RCV002281903.8

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]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002572070Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Aug 15, 2022) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot 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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002572070.1

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

Description

Variant summary: SCN5A c.210T>G (p.Asn70Lys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 247524 control chromosomes. The observed variant frequency is approximately 2.1 fold of the estimated maximal expected allele frequency for a pathogenic variant in SCN5A causing Long QT Syndrome phenotype (2.1e-05), strongly suggesting that the variant is benign. c.210T>G has been reported in the literature as a VUS in settings of multigene panel testing among individuals with Brugada syndrome/arrhythmia/cardiogenetic disorders (example, Kapplinger_2010, van Lint_2019, Kroncke_2018). These report(s) do not provide unequivocal conclusions about a penetrant association of the variant with SCN5A-related disorders. At least one publication reports experimental evidence evaluating an impact on protein function demonstrating a reduction in sodium current density upon co-expression with WT (example, Hoshi_2014). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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

Last Updated: Nov 3, 2024