VCV000048286.53 - ClinVar

NM_000335.5(SCN5A):c.1571C>A (p.Ser524Tyr)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(25)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000335.5(SCN5A):c.1571C>A (p.Ser524Tyr)

Variation ID: 48286 Accession: VCV000048286.53

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3p22.2 3: 38604031 (GRCh38) [ NCBI UCSC ] 3: 38645522 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jun 4, 2015	Oct 20, 2024	Jul 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000335.5:c.1571C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000326.2:p.Ser524Tyr	missense
NM_001099404.2:c.1571C>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001092874.1:p.Ser524Tyr	missense
NM_001099405.2:c.1571C>A	NP_001092875.1:p.Ser524Tyr	missense
NM_001160160.2:c.1571C>A	NP_001153632.1:p.Ser524Tyr	missense
NM_001160161.2:c.1571C>A	NP_001153633.1:p.Ser524Tyr	missense
NM_001354701.2:c.1571C>A	NP_001341630.1:p.Ser524Tyr	missense
NM_198056.3:c.1571C>A	NP_932173.1:p.Ser524Tyr	missense
NC_000003.12:g.38604031G>T
NC_000003.11:g.38645522G>T
NG_008934.1:g.50642C>A
LRG_289:g.50642C>A
LRG_289t1:c.1571C>A	LRG_289p1:p.Ser524Tyr
LRG_289t3:c.1571C>A	LRG_289p3:p.Ser524Tyr
	Q14524:p.Ser524Tyr

... more HGVS ... less HGVS

Protein change

S524Y

Other names

Canonical SPDI

NC_000003.12:38604030:G:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.01138 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00338

Exome Aggregation Consortium (ExAC) 0.00512

1000 Genomes Project 0.01138

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01139

1000 Genomes Project 30x 0.01140

The Genome Aggregation Database (gnomAD) 0.01184

Trans-Omics for Precision Medicine (TOPMed) 0.01186

Links

ClinGen: CA014995 UniProtKB: Q14524#VAR_036663 dbSNP: rs41313691 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
SCN5A		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	3783	4225

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign (4)	criteria provided, multiple submitters, no conflicts	Nov 22, 2014	RCV000041601.24
not provided	Benign/Likely benign (8)	criteria provided, multiple submitters, no conflicts	Jul 1, 2024	RCV000058430.38
Brugada syndrome 1 Long QT syndrome 3	Likely benign (1)	criteria provided, single submitter	Feb 5, 2015	RCV000202694.9
Brugada syndrome Long QT syndrome 3	Benign (1)	criteria provided, single submitter	Nov 24, 2015	RCV000238899.10
Cardiovascular phenotype	Benign (1)	criteria provided, single submitter	Nov 11, 2015	RCV000242695.11
Long QT syndrome 3	Benign (1)	criteria provided, single submitter	Mar 6, 2018	RCV000316117.13
Brugada syndrome 1	Benign (2)	criteria provided, multiple submitters, no conflicts	May 28, 2019	RCV000987230.13
Dilated cardiomyopathy 1E	Likely benign (1)	criteria provided, single submitter	Mar 6, 2018	RCV001144118.12
Sick sinus syndrome 1	Benign (1)	criteria provided, single submitter	Mar 6, 2018	RCV001144119.12
Ventricular fibrillation, paroxysmal familial, type 1	Benign (1)	criteria provided, single submitter	Mar 6, 2018	RCV001144120.12
Progressive familial heart block, type 1A	Likely benign (1)	criteria provided, single submitter	Mar 6, 2018	RCV001146003.12
Cardiac arrhythmia	Benign (1)	criteria provided, single submitter	Mar 15, 2018	RCV001841590.10
Atrial fibrillation, familial, 10 Brugada syndrome 1 Dilated cardiomyopathy 1E Long QT syndrome 3 Progressive familial heart block, type 1A SUDDEN INFANT DEATH SYNDROME Sick sinus syndrome 1 Ventricular fibrillation, paroxysmal familial, type 1	Benign (1)	criteria provided, single submitter	Apr 20, 2022	RCV002496657.8
Cardiomyopathy	Benign (1)	criteria provided, single submitter	Jan 9, 2023	RCV003486622.1
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Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Mar 08, 2018)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV000843705.1 First in ClinVar: Oct 09, 2016 Last updated: Oct 09, 2016	Publications: PubMed (8) PubMed: 16453024‚ 26332594‚ 15992732‚ 17331104‚ 26220391‚ 15851227‚ 23571586‚ 18378609
Benign (Mar 19, 2012)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000065297.6 First in ClinVar: May 03, 2013 Last updated: Oct 02, 2016	Comment: p.Ser524Tyr in Exon 12 of SCN5A: This variant is not expected to have clinical s ignificance because it has been identified in 3.4% (114/3402) of … (more) p.Ser524Tyr in Exon 12 of SCN5A: This variant is not expected to have clinical s ignificance because it has been identified in 3.4% (114/3402) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs41313691). (less) Number of individuals with the variant: 23
Benign (Apr 20, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Progressive familial heart block, type 1A SUDDEN INFANT DEATH SYNDROME Brugada syndrome 1 Dilated cardiomyopathy 1E Ventricular fibrillation, paroxysmal familial, type 1 Long QT syndrome 3 Sick sinus syndrome 1 Atrial fibrillation, familial, 10 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002813754.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Benign (Apr 22, 2020)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001944441.2 First in ClinVar: Sep 29, 2021 Last updated: Mar 04, 2023	Comment: This variant is associated with the following publications: (PMID: 31043699, 15992732, 16453024, 26332594, 32880476)
Benign (Jan 09, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cardiomyopathy Affected status: unknown Allele origin: germline	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario Accession: SCV004239650.1 First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000291780.9 First in ClinVar: Jul 01, 2016 Last updated: Feb 28, 2024
Benign (Jul 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV002585972.15 First in ClinVar: Oct 22, 2022 Last updated: Oct 20, 2024	Comment: SCN5A: BP4, BS1, BS2 Number of individuals with the variant: 19
Benign (Jun 24, 2013)	criteria provided, single submitter (Ng et al. (Circ Cardiovasc Genet. 2013)) Method: research	not specified Affected status: unknown Allele origin: unknown	Biesecker Lab/Clinical Genomics Section, National Institutes of Health Study: ClinSeq Accession: SCV000050840.1 First in ClinVar: Jun 04, 2015 Last updated: Jun 04, 2015 Comments (2): The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for … (more) The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for details. (less) Medical sequencing	Number of individuals with the variant: 1
Likely benign (Feb 05, 2015)	criteria provided, single submitter (DGD Variant Analysis Guidelines) Method: clinical testing	Brugada syndrome 1 Long QT syndrome 3 Affected status: unknown Allele origin: unknown	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia Accession: SCV000257777.2 First in ClinVar: Dec 27, 2015 Last updated: Dec 27, 2015
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000306535.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Nov 22, 2014)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000225723.5 First in ClinVar: Jun 28, 2015 Last updated: Oct 02, 2016	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SCN5A Number of individuals with the variant: 1 Sex: mixed
Benign (Mar 15, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Arrhythmia Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000903048.1 First in ClinVar: May 20, 2019 Last updated: May 20, 2019
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: yes Allele origin: germline	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute Accession: SCV000987366.1 First in ClinVar: Sep 06, 2019 Last updated: Sep 06, 2019
Benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Brugada syndrome 1 Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001136479.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Benign (Mar 06, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Sick sinus syndrome 1 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001304698.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (Mar 06, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Ventricular fibrillation, paroxysmal familial, type 1 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001304699.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Likely benign (Mar 06, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Dilated cardiomyopathy 1E Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001304697.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
Benign (Mar 06, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Brugada syndrome 1 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001306715.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Likely benign (Mar 06, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Progressive familial heart block, type 1A Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001306716.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
Benign (Mar 06, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Long QT syndrome 3 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000444146.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (Nov 24, 2015)	criteria provided, single submitter (DGD Variant Analysis Guidelines) Method: clinical testing	Brugada syndrome Long QT syndrome 3 Affected status: unknown Allele origin: unknown	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia Accession: SCV000297007.3 First in ClinVar: Jul 31, 2016 Last updated: Dec 24, 2022
Benign (Mar 30, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV001474118.2 First in ClinVar: Jan 26, 2021 Last updated: Feb 20, 2024
Benign (Nov 11, 2015)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cardiovascular phenotype Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000320011.7 First in ClinVar: Oct 02, 2016 Last updated: May 01, 2024	Comment: This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more) This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005258489.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
not provided (-)	no classification provided Method: literature only	not provided Affected status: unknown Allele origin: germline	Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust Accession: SCV000089950.3 First in ClinVar: Oct 22, 2013 Last updated: Oct 09, 2016	Publications: PubMed (5) PubMed: 22581653‚ 19841300‚ 20129283‚ 16453024‚ 15992732 Comment: This variant has been reported in the following publications (PMID:19841300;PMID:20129283;PMID:16453024;PMID:15992732).
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Comment:

p.Ser524Tyr in Exon 12 of SCN5A: This variant is not expected to have clinical s ignificance because it has been identified in 3.4% (114/3402) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs41313691).

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

Comment:

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Identification of Medically Actionable Secondary Findings in the 1000 Genomes.	Olfson E	PloS one	2015	PMID: 26332594
Complex SCN8A DNA-abnormalities in an individual with therapy resistant absence epilepsy.	Berghuis B	Epilepsy research	2015	PMID: 26220391
Long QT syndrome-associated mutations in intrauterine fetal death.	Crotti L	JAMA	2013	PMID: 23571586
An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing.	Kapplinger JD	Heart rhythm	2010	PMID: 20129283
Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants.	Kapa S	Circulation	2009	PMID: 19841300
Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation.	Darbar D	Circulation	2008	PMID: 18378609
A common SCN5A variant alters the responsiveness of human sodium channels to class I antiarrhythmic agents.	Shuraih M	Journal of cardiovascular electrophysiology	2007	PMID: 17331104
A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y.	Plant LD	The Journal of clinical investigation	2006	PMID: 16453024
Common human SCN5A polymorphisms have altered electrophysiology when expressed in Q1077 splice variants.	Tan BH	Heart rhythm	2005	PMID: 15992732
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	Heart rhythm	2004	PMID: 15851227
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SCN5A	-	-	-	-
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Text-mined citations for rs41313691 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 10, 2024

ClinVar Genomic variation as it relates to human health

NM_000335.5(SCN5A):c.1571C>A (p.Ser524Tyr)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs41313691 ...