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NM_000335.5(SCN5A):c.1558A>G (p.Met520Val) AND Cardiac arrhythmia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 18, 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:
RCV003591849.1

Allele description [Variation Report for NM_000335.5(SCN5A):c.1558A>G (p.Met520Val)]

NM_000335.5(SCN5A):c.1558A>G (p.Met520Val)

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.1558A>G (p.Met520Val)
HGVS:
  • NC_000003.12:g.38604044T>C
  • NG_008934.1:g.50629A>G
  • NM_000335.5:c.1558A>GMANE SELECT
  • NM_001099404.2:c.1558A>G
  • NM_001099405.2:c.1558A>G
  • NM_001160160.2:c.1558A>G
  • NM_001160161.2:c.1558A>G
  • NM_001354701.2:c.1558A>G
  • NM_198056.3:c.1558A>G
  • NP_000326.2:p.Met520Val
  • NP_001092874.1:p.Met520Val
  • NP_001092875.1:p.Met520Val
  • NP_001153632.1:p.Met520Val
  • NP_001153633.1:p.Met520Val
  • NP_001341630.1:p.Met520Val
  • NP_932173.1:p.Met520Val
  • LRG_289t1:c.1558A>G
  • LRG_289:g.50629A>G
  • NC_000003.11:g.38645535T>C
  • NC_000003.11:g.38645535T>C
  • NM_198056.2:c.1558A>G
Protein change:
M520V
Links:
dbSNP: rs769799503
NCBI 1000 Genomes Browser:
rs769799503
Molecular consequence:
  • NM_000335.5:c.1558A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.1558A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.1558A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.1558A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.1558A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.1558A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.1558A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV004361712Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Nov 18, 2021) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Novel genotype-electroclinical phenotype correlations in sporadic early-onset childhood myoclonic-atonic epilepsy.

Babu SP, Menon RN, Asranna A, Nampoothiri S, Radhakrishnan A, Cherian A, Thomas SV.

Neurol India. 2019 Jan-Feb;67(1):264-267. doi: 10.4103/0028-3886.253628. No abstract available.

PubMed [citation]
PMID:
30860130

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV004361712.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This missense variant replaces methionine with valine at codon 520 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with myoclonic-atonic epilepsy (PMID: 30860130). This variant has also been identified in 9/268438 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

Last Updated: Nov 10, 2024