ClinVar Genomic variation as it relates to human health
NM_000335.5(SCN5A):c.4531C>T (p.Arg1511Trp)
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.
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.
Likely pathogenic(5); Uncertain significance(6)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000335.5(SCN5A):c.4531C>T (p.Arg1511Trp)
Variation ID: 9380 Accession: VCV000009380.31
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p22.2 3: 38555664 (GRCh38) [ NCBI UCSC ] 3: 38597155 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Feb 6, 2015 Feb 20, 2024 Dec 15, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000335.5:c.4531C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000326.2:p.Arg1511Trp missense NM_001099404.2:c.4534C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001092874.1:p.Arg1512Trp missense NM_001099405.2:c.4480C>T NP_001092875.1:p.Arg1494Trp missense NM_001160160.2:c.4531C>T NP_001153632.1:p.Arg1511Trp missense NM_001160161.2:c.4372C>T NP_001153633.1:p.Arg1458Trp missense NM_001354701.2:c.4477C>T NP_001341630.1:p.Arg1493Trp missense NM_198056.3:c.4534C>T NP_932173.1:p.Arg1512Trp missense NC_000003.12:g.38555664G>A NC_000003.11:g.38597155G>A NG_008934.1:g.99009C>T LRG_289:g.99009C>T LRG_289t1:c.4534C>T LRG_289p1:p.Arg1512Trp LRG_289t3:c.4534C>T LRG_289p3:p.Arg1512Trp - Protein change
- R1512W, R1511W, R1493W, R1494W, R1458W
- Other names
- p.R1512W:CGG>TGG
- Canonical SPDI
- NC_000003.12:38555663:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00006
Exome Aggregation Consortium (ExAC) 0.00007
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 | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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. |
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SCN5A | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3554 | 3958 |
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. |
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Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Aug 30, 2018 | RCV000009977.16 | |
Conflicting interpretations of pathogenicity (7) |
criteria provided, conflicting classifications
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Dec 4, 2023 | RCV000058688.25 | |
Uncertain significance (1) |
no assertion criteria provided
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Jul 18, 2014 | RCV000157490.9 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Dec 15, 2023 | RCV000222521.15 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jun 16, 2023 | RCV001841232.11 |
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. |
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Likely pathogenic
(Jan 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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Brugada syndrome 1
Affected status: yes
Allele origin:
germline
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Center for Medical Genetics Ghent, University of Ghent
Accession: SCV000299258.1
First in ClinVar: Sep 09, 2016 Last updated: Sep 09, 2016 |
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Uncertain significance
(Jan 29, 2019)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000272416.4
First in ClinVar: May 29, 2016 Last updated: Jul 03, 2020 |
Comment:
Variant classified as Uncertain Significance - Favor Pathogenic. The p.Arg1512Trp variant in SCN5A has been reported in 7 individuals with features of arrhythmia, sudden death, … (more)
Variant classified as Uncertain Significance - Favor Pathogenic. The p.Arg1512Trp variant in SCN5A has been reported in 7 individuals with features of arrhythmia, sudden death, Brugada syndrome and/or LQTS (Rook 1999, Deschênes 2000, Meregalli 2009, Cheng 2011, Crotti 2012, Chiang 2015) and in 1 individual with infantile onset of LV dysfunction (LMM data). It has been identified in 9/33552 Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs137854602). This variant is present in ClinVar (Variation ID: 9380). In vitro functional studies provide some evidence that the variant may impact protein function (Rook 1999, Deschênes 2000, Zheng 2016). However, these types of assays may not accurately represent biological function. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while there is some suspicion for a pathogenic role, the clinical significance of the p.Arg1512Trp variant is uncertain. (less)
Number of individuals with the variant: 1
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Uncertain significance
(May 28, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001470836.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
Comment:
The SCN5A c.4534C>T; p.Arg1512Trp variant (rs137854602) is reported in the literature in multiple individuals affected with Brugada syndrome, cardiac conduction disease, or sudden unexpected death … (more)
The SCN5A c.4534C>T; p.Arg1512Trp variant (rs137854602) is reported in the literature in multiple individuals affected with Brugada syndrome, cardiac conduction disease, or sudden unexpected death (Cheng 2011, Chiang 2015, Crotti 2012, Deschenes 2000, Meregalli 2009, Rook 1999), although it has also been observed in a healthy control (Ackerman 2004, Kapplinger 2010). This variant is found in the general population with an overall allele frequency of 0.006% (14/251272 alleles) in the Genome Aggregation Database and is reported in ClinVar (Variation ID: 9380). The arginine at codon 1512 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Functional analyses consistently indicate a slower recovery from inactivation (Deschenes 2000, Rook 1999, Zheng 2016), but also report conflicting mechanisms. While one report indicates a gain-of-function mechanism marked by increased excitability and lower action potential threshold (Rook 1999), several other studies report loss-of-function characterized by reduced peak sodium current (Deschenes 2000, Zheng 2016), which is exacerbated under acidosis conditions (Zheng 2016). While it is possible that the p.Arg1512Trp variant is associated with disease with reduced penetrance, due to incomplete and conflicting information, its clinical significance remains uncertain at this time. (less)
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Uncertain significance
(Dec 15, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004226068.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PP3, PM6
Number of individuals with the variant: 1
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Likely pathogenic
(Jul 06, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003812650.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Likely pathogenic
(Aug 30, 2018)
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criteria provided, single submitter
Method: clinical testing
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BRUGADA SYNDROME 1
Affected status: yes
Allele origin:
germline
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Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV000996193.1
First in ClinVar: Oct 19, 2019 Last updated: Oct 19, 2019 |
Comment:
This variant has been previously reported by multiple clinical labs as pathogenic or likely pathogenic according to the ClinVar database. One clinical lab reports p.Arg1512Trp … (more)
This variant has been previously reported by multiple clinical labs as pathogenic or likely pathogenic according to the ClinVar database. One clinical lab reports p.Arg1512Trp as a variant of uncertain significance. Additionally, there multiple reports in the literature of the variant in patients diagnosed with Brugada Syndrome and arrhythmias (PMID: 10690282, 10727653, 19251209, 20110800, 26111534, 27281089). This variant was identified in a healthy adult in one publication (PMID: 15851227). Functional studies characterizing the effect of the variant on protein function demonstrates altered channel gating dynamics relative to the reference allele. Deschenes et al. demonstrated that p.Arg1512Trp results in loss of function, producing a slowing of both inactivation and recovery from inactivation (PMID: 10727653). Rook et al. found p.Arg1512Trp resulted in moderate kinetic alterations including a negative voltage shift of steady-state activation and inactivation curves (PMID: 10690282). More recently, Zheng et al. identified a de novo p.Arg1512Trp variant in a 38 year old Chinese patient with tachypnea and sudden unexplained noctural death (SUNDS)(PMID: 27281089). These authors also demonstrated a more deleterious effect of the variant under slightly acidic conditions (pH 7.0 versus pH 7.4). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.004% (12/246090) and thus is presumed to be rare. The p.Arg1512Trp variant is a non-conservative amino acid substitution predicted to be damaging by multiple in silico tools and the amino acid residue is highly conserved among eukaryotes. Based on the available evidence, the c.4534C>T (p.Arg1512Trp) variant is classified as likely pathogenic. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Mar 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000235490.13
First in ClinVar: Jul 05, 2015 Last updated: Apr 23, 2023 |
Comment:
Reported in multiple individuals with Brugada syndrome or sudden unexplained nocturnal death (SUND) (Cheng et al., 2011; Crotti et al., 2012; Liu et al., 2014; … (more)
Reported in multiple individuals with Brugada syndrome or sudden unexplained nocturnal death (SUND) (Cheng et al., 2011; Crotti et al., 2012; Liu et al., 2014; Meregalli et al., 2009; Deschnes et al., 2000; Berthome et al., 2019; LeScouarnec et al., 2015; Zhang et al., 2021), and reported in at least one healthy control individual (Kapa et al., 2009; Kapplinger et al., 2010; Crotti et al., 2012; Ackerman et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate a damaging effect (Deschenes et al., 2000; Rook et al., 1999; Zheng et al., 2016; Hu et al., 2021), however, they propose different mechanisms of disease, and additional studies are needed to validate the functional effect of this variant in vivo; This variant is associated with the following publications: (PMID: 28518168, 26111534, 19251209, 34649698, 15851227, 27281089, 19841300, 22840528, 24529773, 10727653, 33221895, 33535892, 30662450, 31564432, 32268277, 30193851, 33131149, 25650408, 20486126, 20129283, 10690282, 20110800, 35911527, 36516610, 36435694, 34461752, 34546463, 36007526, 35124229) (less)
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Likely pathogenic
(Jun 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Athena Diagnostics Inc
Accession: SCV004230022.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Comment:
This variant is statistically more frequent in affected individuals than in the general population and/or healthy controls (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)). … (more)
This variant is statistically more frequent in affected individuals than in the general population and/or healthy controls (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)). This variant has been identified in multiple individuals with clinical features of Brugada syndrome, and appeared to occur de novo in an individual with sudden unexplained nocturnal death syndrome (SUNDS). In some published literature, this variant is referred to as c.4372C>T, p.Arg1458Trp. Computational tools predict that this variant is damaging. (less)
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Uncertain significance
(Dec 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004241184.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
Comment:
Variant summary: SCN5A c.4534C>T (p.Arg1512Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Variant summary: SCN5A c.4534C>T (p.Arg1512Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.3e-05 in 255630 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in SCN5A causing Brugada Syndrome (6.3e-05 vs 0.00017), allowing no conclusion about variant significance. c.4534C>T has been reported in the literature in individuals affected with Brugada Syndrome and sudden death (eg. Rook_1999, Deschenes_2000, Cheng_2011, Meregalli_2009, Chiang_2016), including one report in a healthy individual (Crotti_2012), a patient who carried a known pathogenic SCN5A variant (Zhang_2022), in a 38 year old with sudden death in whom the variant was reported to be de novo (Zheng_2016), and from an exome sequencing trio inherited from the mother (Kingsmore_2019). These data indicate that the variant may be associated with disease. Functional studies have demonstrated various damaging impacts of the variant. These impacts include slowed inactivation and recovery from inactivation (Deschenes_2000), a moderate alteration in kinetics including a negative voltage shift of steady-state activation and inactivation curves (Rook_1999) and a more damaging effect was seen under slightly acidic conditions (Zheng_2016). However, it is unclear what how well these impacts represent the biological impact of the variant. The following publications have been ascertained in the context of this evaluation (PMID: 15851227, 14961552, 20129283, 20486126, 22840528, 24529773, 10727653, 19251209, 10690282, 26111534, 27281089, 31564432, 34649698, 20110800). Eight submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Multiple submitters reported the variant with conflicting assessments: four submitters classified the variant as VUS while four classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS - possibly pathogenic. (less)
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Uncertain significance
(Jun 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Cardiac arrhythmia
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV001351146.3
First in ClinVar: Jun 22, 2020 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces arginine with tryptophan at codon 1512 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
This missense variant replaces arginine with tryptophan at codon 1512 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). Functional studies have shown that this variant results in altered cardiac sodium channel characteristics, reduced peak sodium current, and decreased cell surface expression of the channel (PMID: 10690282, 10727653, 27281089, 33535892). This variant has been reported in individuals affected with Brugada syndrome (PMID: 10690282, 10727653, 19251209, 20486126, 25650408, 30193851, 36516610, 37061847), sudden death (PMID: 20110800, 24529773, 26111534), as well as in healthy control individuals (PMID: 15851227,19841300, 20129283, 22840528). This variant has been identified in 14/251272 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. (less)
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Likely pathogenic
(Dec 04, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000545007.7
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1512 of the SCN5A protein … (more)
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1512 of the SCN5A protein (p.Arg1512Trp). This variant is present in population databases (rs137854602, gnomAD 0.03%). This missense change has been observed in individuals with clinical features of Brugada syndrome (PMID: 10690282, 15851227, 20110800, 20486126, 22840528, 24529773, 25650408, 26111534). ClinVar contains an entry for this variant (Variation ID: 9380). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects SCN5A function (PMID: 10690282, 10727653). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
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Pathogenic
(Dec 01, 1999)
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no assertion criteria provided
Method: literature only
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BRUGADA SYNDROME 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000030198.2
First in ClinVar: Apr 04, 2013 Last updated: Nov 14, 2016 |
Comment on evidence:
In the screening of SCN5A in 6 individuals with Brugada syndrome (BRGDA1; 601144), Rook et al. (1999) found missense mutations in the coding region of … (more)
In the screening of SCN5A in 6 individuals with Brugada syndrome (BRGDA1; 601144), Rook et al. (1999) found missense mutations in the coding region of the gene in 2: arg1512 to trp (R1512W) in the DIII-DIV cytoplasmic linker, and ala1924 to thr (A1924T; 600163.0012) in the C-terminal cytoplasmic domain. In 2 other patients mutations were detected near intron/exon junctions. To assess the functional consequences of the R1512W and A1924T mutations, wildtype and mutant sodium channel proteins were expressed in Xenopus oocytes. Both missense mutations affected channel function and seemed to be associated with an increase in inward sodium current during the action potential upstroke. (less)
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Uncertain significance
(Jul 18, 2014)
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no assertion criteria provided
Method: clinical testing
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Primary familial hypertrophic cardiomyopathy
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV000207235.1
First in ClinVar: Feb 06, 2015 Last updated: Feb 06, 2015 |
Number of individuals with the variant: 1
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not provided
(-)
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no classification provided
Method: literature only
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not provided
Affected status: unknown
Allele origin:
germline
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Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust
Accession: SCV000090208.3
First in ClinVar: Oct 22, 2013 Last updated: Oct 09, 2016 |
Comment:
This variant has been reported in the following publications (PMID:10690282;PMID:10727653;PMID:15851227;PMID:19251209;PMID:19841300;PMID:20129283).
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Genetic testing in children with Brugada syndrome: results from a large prospective registry. | Pannone L | Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology | 2023 | PMID: 37061847 |
Clinical characteristics and electrophysiologic properties of SCN5A variants in fever-induced Brugada syndrome. | Chen GX | EBioMedicine | 2023 | PMID: 36516610 |
A genome sequencing system for universal newborn screening, diagnosis, and precision medicine for severe genetic diseases. | Kingsmore SF | American journal of human genetics | 2022 | PMID: 36007526 |
SCN5A mutation in Brugada syndrome is associated with substrate severity detected by electrocardiographic imaging and high-density electroanatomic mapping. | Pannone L | Heart rhythm | 2022 | PMID: 35124229 |
Clinical impact of rare variants associated with inherited channelopathies: a 5-year update. | Sarquella-Brugada G | Human genetics | 2022 | PMID: 34546463 |
Distinct Features of Probands With Early Repolarization and Brugada Syndromes Carrying SCN5A Pathogenic Variants. | Zhang ZH | Journal of the American College of Cardiology | 2021 | PMID: 34649698 |
Artificial intelligence enables comprehensive genome interpretation and nomination of candidate diagnoses for rare genetic diseases. | De La Vega FM | Genome medicine | 2021 | PMID: 34645491 |
Genotype-Phenotype Correlation of SCN5A Genotype in Patients With Brugada Syndrome and Arrhythmic Events: Insights From the SABRUS in 392 Probands. | Milman A | Circulation. Genomic and precision medicine | 2021 | PMID: 34461752 |
Expression defect of the rare variant/Brugada mutation R1512W depends upon the SCN5A splice variant background and can be rescued by mexiletine and the common polymorphism H558R. | Hu RM | Channels (Austin, Tex.) | 2021 | PMID: 33535892 |
Brugada syndrome genetics is associated with phenotype severity. | Ciconte G | European heart journal | 2021 | PMID: 33221895 |
Relationship between sodium channel function and clinical phenotype in SCN5A variants associated with Brugada syndrome. | Pearman CM | Human mutation | 2020 | PMID: 33131149 |
A Randomized, Controlled Trial of the Analytic and Diagnostic Performance of Singleton and Trio, Rapid Genome and Exome Sequencing in Ill Infants. | Kingsmore SF | American journal of human genetics | 2019 | PMID: 31564432 |
Clinical presentation and follow-up of women affected by Brugada syndrome. | Berthome P | Heart rhythm | 2019 | PMID: 30193851 |
Using high-resolution variant frequencies to empower clinical genome interpretation. | Whiffin N | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 28518168 |
Loss-of-Function SCN5A Mutations Associated With Sinus Node Dysfunction, Atrial Arrhythmias, and Poor Pacemaker Capture. | Chiang DY | Circulation. Arrhythmia and electrophysiology | 2015 | PMID: 26111534 |
Testing the burden of rare variation in arrhythmia-susceptibility genes provides new insights into molecular diagnosis for Brugada syndrome. | Le Scouarnec S | Human molecular genetics | 2015 | PMID: 25650408 |
Is sudden unexplained nocturnal death syndrome in Southern China a cardiac sodium channel dysfunction disorder? | Liu C | Forensic science international | 2014 | PMID: 24529773 |
Spectrum and prevalence of mutations involving BrS1- through BrS12-susceptibility genes in a cohort of unrelated patients referred for Brugada syndrome genetic testing: implications for genetic testing. | Crotti L | Journal of the American College of Cardiology | 2012 | PMID: 22840528 |
Sudden unexplained nocturnal death syndrome in Southern China: an epidemiological survey and SCN5A gene screening. | Cheng J | The American journal of forensic medicine and pathology | 2011 | PMID: 20110800 |
A new approach to long QT syndrome mutation detection by Sequenom MassARRAY system. | Allegue C | Electrophoresis | 2010 | PMID: 20486126 |
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 |
Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies. | Meregalli PG | Heart rhythm | 2009 | PMID: 19251209 |
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 |
Sodium channel gene (SCN5A) mutations in 44 index patients with Brugada syndrome: different incidences in familial and sporadic disease. | Schulze-Bahr E | Human mutation | 2003 | PMID: 14961552 |
Electrophysiological characterization of SCN5A mutations causing long QT (E1784K) and Brugada (R1512W and R1432G) syndromes. | Deschênes I | Cardiovascular research | 2000 | PMID: 10727653 |
Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome. | Rook MB | Cardiovascular research | 1999 | PMID: 10690282 |
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HelpRecord last updated Mar 17, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.