NM_000335.5(SCN5A):c.6013C>G (p.Pro2005Ala) AND Brugada syndrome 1

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Mar 23, 2018
Review status:: criteria provided, conflicting classifications

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:: RCV000678920.16

Allele description [Variation Report for NM_000335.5(SCN5A):c.6013C>G (p.Pro2005Ala)]

NM_000335.5(SCN5A):c.6013C>G (p.Pro2005Ala)

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.6013C>G (p.Pro2005Ala)

Other names:

p.P2006A:CCT>GCT

HGVS:

NC_000003.12:g.38550356G>C
NG_008934.1:g.104317C>G
NM_000335.5:c.6013C>GMANE SELECT
NM_001099404.1:c.6016C>G
NM_001099404.2:c.6016C>G
NM_001099405.2:c.5962C>G
NM_001160160.2:c.5917C>G
NM_001160161.2:c.5854C>G
NM_001354701.2:c.5959C>G
NM_198056.3:c.6016C>G
NP_000326.2:p.Pro2005Ala
NP_001092874.1:p.Pro2006Ala
NP_001092875.1:p.Pro1988Ala
NP_001153632.1:p.Pro1973Ala
NP_001153633.1:p.Pro1952Ala
NP_001341630.1:p.Pro1987Ala
NP_932173.1:p.Pro2006Ala
NP_932173.1:p.Pro2006Ala
LRG_289t1:c.6016C>G
LRG_289t3:c.6016C>G
LRG_289:g.104317C>G
LRG_289p1:p.Pro2006Ala
NC_000003.11:g.38591847G>C
NM_198056.2:c.6016C>G
Q14524:p.Pro2006Ala

Protein change:

P1952A

Links:

UniProtKB: Q14524#VAR_055222; dbSNP: rs45489199

NCBI 1000 Genomes Browser:

rs45489199

Molecular consequence:

NM_000335.5:c.6013C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.6016C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.5962C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.5917C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.5854C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.5959C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.6016C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Brugada syndrome 1 (BRGDA1)
Synonyms:: Right bundle branch block, ST segment elevation, and sudden death syndrome
Identifiers:: MONDO: MONDO:0011001; MedGen: C4551804; Orphanet: 130; OMIM: 601144

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000805127	Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 27, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001310898	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Mar 23, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15851227, 26159999, 20129283 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000805127

Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 27, 2017)

unknown

clinical testing

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

SCV001310898

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Mar 23, 2018)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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
not provided	unknown	yes	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

Spectrum and prevalence of cardiac sodium channel variants among black, white, Asian, and Hispanic individuals: implications for arrhythmogenic susceptibility and Brugada/long QT syndrome genetic testing.

Ackerman MJ, Splawski I, Makielski JC, Tester DJ, Will ML, Timothy KW, Keating MT, Jones G, Chadha M, Burrow CR, Stephens JC, Xu C, Judson R, Curran ME.

Heart Rhythm. 2004 Nov;1(5):600-7.

PubMed [citation]

PMID:: 15851227

See all PubMed Citations (4)

Details of each submission

From Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues, SCV000805127.1

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

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

From Illumina Laboratory Services, Illumina, SCV001310898.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

#	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: Apr 20, 2024

ClinVar

Relating variation to medicine