NM_000335.5(SCN5A):c.4864C>T (p.Arg1622Ter) AND Arrhythmia

delete

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 7, 2019
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:: RCV001188430.2

Allele description

NM_000335.5(SCN5A):c.4864C>T (p.Arg1622Ter)

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.4864C>T (p.Arg1622Ter)

Other names:

p.R1623*:CGA>TGA

HGVS:

NC_000003.12:g.38551505G>A
NG_008934.1:g.103168C>T
NM_000335.5:c.4864C>TMANE SELECT
NM_001099404.2:c.4867C>T
NM_001099405.2:c.4813C>T
NM_001160160.2:c.4768C>T
NM_001160161.2:c.4705C>T
NM_001354701.2:c.4810C>T
NM_198056.3:c.4867C>T
NP_000326.2:p.Arg1622Ter
NP_001092874.1:p.Arg1623Ter
NP_001092874.1:p.Arg1623Ter
NP_001092875.1:p.Arg1605Ter
NP_001153632.1:p.Arg1590Ter
NP_001153633.1:p.Arg1569Ter
NP_001341630.1:p.Arg1604Ter
NP_932173.1:p.Arg1623Ter
NP_932173.1:p.Arg1623Ter
LRG_289t1:c.4867C>T
LRG_289t3:c.4867C>T
LRG_289:g.103168C>T
LRG_289p1:p.Arg1623Ter
LRG_289p3:p.Arg1623Ter
NC_000003.11:g.38592996G>A
NM_001099404.1:c.4867C>T
NM_198056.2:c.4867C>T

Protein change:

R1569*; ARG1623TER

Links:

OMIM: 600163.0028; dbSNP: rs137854613

NCBI 1000 Genomes Browser:

rs137854613

Molecular consequence:

NM_000335.5:c.4864C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001099404.2:c.4867C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001099405.2:c.4813C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001160160.2:c.4768C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001160161.2:c.4705C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354701.2:c.4810C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_198056.3:c.4867C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Arrhythmia
Identifiers:: EFO: EFO_0004269; MedGen: C0855329; Human Phenotype Ontology: HP:0011675

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001355489	Color Health, Inc	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 7, 2019)	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

SCV001355489

Color Health, Inc

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 7, 2019)

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 Health, Inc, SCV001355489.2

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

Description

This variant changes 1 nucleotide in exon 28 of the SCN5A gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Functional studies have shown that this variant results in the loss of detectable inward sodium current (PMID: 16325048, 20539757). This variant has been reported in two individuals affected with Brugada syndrome (PMID: 15840483, 16325048), in an individual affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 28069705), and in a pediatric proband affected with sudden cardiac arrest and death (PMID: 26187847). This variant has also been observed in compound heterozygosity with p.Thr220Ile in an individual affected with congenital sick sinus syndrome (PMID: 14523039). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of function is a known mechanism of disease for the SCN5A gene. Based on the available evidence, this variant is classified as Pathogenic.

#	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: Feb 26, 2022

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