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NM_000335.5(SCN5A):c.4807G>A (p.Val1603Met) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 11, 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:
RCV001328334.10

Allele description [Variation Report for NM_000335.5(SCN5A):c.4807G>A (p.Val1603Met)]

NM_000335.5(SCN5A):c.4807G>A (p.Val1603Met)

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.4807G>A (p.Val1603Met)
HGVS:
  • NC_000003.12:g.38554282C>T
  • NG_008934.1:g.100391G>A
  • NM_000335.5:c.4807G>AMANE SELECT
  • NM_001099404.2:c.4810G>A
  • NM_001099405.2:c.4756G>A
  • NM_001160160.2:c.4714+93G>A
  • NM_001160161.2:c.4648G>A
  • NM_001354701.2:c.4753G>A
  • NM_198056.3:c.4810G>A
  • NP_000326.2:p.Val1603Met
  • NP_001092874.1:p.Val1604Met
  • NP_001092875.1:p.Val1586Met
  • NP_001153633.1:p.Val1550Met
  • NP_001341630.1:p.Val1585Met
  • NP_932173.1:p.Val1604Met
  • NP_932173.1:p.Val1604Met
  • LRG_289t1:c.4810G>A
  • LRG_289:g.100391G>A
  • LRG_289p1:p.Val1604Met
  • NC_000003.11:g.38595773C>T
  • NM_198056.2:c.4810G>A
  • Q14524:p.Val1604Met
Protein change:
V1550M
Links:
UniProtKB: Q14524#VAR_074458; dbSNP: rs199473280
NCBI 1000 Genomes Browser:
rs199473280
Molecular consequence:
  • NM_001160160.2:c.4714+93G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000335.5:c.4807G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.4810G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.4756G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.4648G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.4753G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.4810G>A - 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
SCV001519410Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Mar 11, 2021) 		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

Impact of Ancestral Differences and Reassessment of the Classification of Previously Reported Pathogenic Variants in Patients With Brugada Syndrome in the Genomic Era: A SADS-TW BrS Registry.

Chen CJ, Lu TP, Lin LY, Liu YB, Ho LT, Huang HC, Lai LP, Hwang JJ, Yeh SS, Wu CK, Juang JJ, Antzelevitch C.

Front Genet. 2018;9:680. doi: 10.3389/fgene.2018.00680.

PubMed [citation]
PMID:
30662450
PMCID:
PMC6328444
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001519410.1

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

Description

Variant summary: SCN5A c.4810G>A (p.Val1604Met) results in a conservative amino acid change located in the Ion transport domain (IPR005821) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 246326 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4810G>A has been reported in the literature in individuals affected with Brugada Syndrome and Dilated Cardiomyopathy without strong evidence for causality (e.g. Kapplinger_2010, Xiong_2015, Berthome_2018). These reports do not provide unequivocal conclusions about association of the variant with Arrhythmia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Oct 20, 2024