NM_000335.5(SCN5A):c.246C>G (p.Asp82Glu) AND Cardiac arrhythmia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 23, 2020
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:: RCV001842580.10

Allele description [Variation Report for NM_000335.5(SCN5A):c.246C>G (p.Asp82Glu)]

NM_000335.5(SCN5A):c.246C>G (p.Asp82Glu)

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.246C>G (p.Asp82Glu)

Other names:

p.Asp82Glu

HGVS:

NC_000003.12:g.38633062G>C
NG_008934.1:g.21611C>G
NM_000335.5:c.246C>GMANE SELECT
NM_001099404.1:c.246C>G
NM_001099404.2:c.246C>G
NM_001099405.2:c.246C>G
NM_001160160.2:c.246C>G
NM_001160161.2:c.246C>G
NM_001354701.2:c.246C>G
NM_198056.3:c.246C>G
NP_000326.2:p.Asp82Glu
NP_001092874.1:p.Asp82Glu
NP_001092875.1:p.Asp82Glu
NP_001153632.1:p.Asp82Glu
NP_001153633.1:p.Asp82Glu
NP_001341630.1:p.Asp82Glu
NP_932173.1:p.Asp82Glu
NP_932173.1:p.Asp82Glu
LRG_289t1:c.246C>G
LRG_289t3:c.246C>G
LRG_289:g.21611C>G
LRG_289p1:p.Asp82Glu
NC_000003.11:g.38674553G>C
NC_000003.11:g.38674553G>C
NM_198056.2:c.246C>G

Protein change:

D82E

Links:

dbSNP: rs747643709

NCBI 1000 Genomes Browser:

rs747643709

Molecular consequence:

NM_000335.5:c.246C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.246C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.246C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.246C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.246C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.246C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.246C>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
SCV001342083	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 23, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001342083

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 23, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV001342083.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This missense variant replaces aspartic acid with glutamic acid at codon 82 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 3/237766 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: Oct 26, 2024

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