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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004361712	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 18, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30860130, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004361712

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 18, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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