The Phe1293Ser variant in SCN5A has been reported in 2 individuals with Brugada syndrome (Priori 2002, Sommariva 2012), one of whom carried a frameshift variant in the other copy of SCN5A, but has also been identified in 1/590 Caucasian con trol chromosomes (Ackerman 2004) and in 4/8412 European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/; dbSNP rs41311 127). This variant has also been identified by our laboratory in 1 Caucasian ind ividual with DCM, who had a pathogenic variant in a different gene. The affected amino acid is poorly conserved in evolution, raising the possibility that a cha nge at this position would be tolerated. Other computational prediction tools do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the Phe1293Ser variant is uncertain.
ClinVar Genomic variation as it relates to human health
NM_000335.5(SCN5A):c.3875T>C (p.Phe1292Ser)
Germline
Classification
Help
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.
(16)
Help
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.
Conflicting classifications of pathogenicity
Uncertain significance(4); Benign(1); Likely benign(8)
Uncertain significance(4); Benign(1); Likely benign(8)
16
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000335.5(SCN5A):c.3875T>C (p.Phe1292Ser)
Variation ID: 67833 Accession: VCV000067833.52
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 3p22.2 3: 38562500 (GRCh38) [ NCBI UCSC ] 3: 38603991 (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 Jan 30, 2015 Nov 3, 2024 May 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000335.5:c.3875T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000326.2:p.Phe1292Ser missense NM_001099404.2:c.3878T>C MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001092874.1:p.Phe1293Ser missense NM_001099405.2:c.3878T>C NP_001092875.1:p.Phe1293Ser missense NM_001160160.2:c.3875T>C NP_001153632.1:p.Phe1292Ser missense NM_001160161.2:c.3716T>C NP_001153633.1:p.Phe1239Ser missense NM_001354701.2:c.3875T>C NP_001341630.1:p.Phe1292Ser missense NM_198056.3:c.3878T>C NP_932173.1:p.Phe1293Ser missense NC_000003.12:g.38562500A>G NC_000003.11:g.38603991A>G NG_008934.1:g.92173T>C LRG_289:g.92173T>C LRG_289t1:c.3878T>C LRG_289p1:p.Phe1293Ser LRG_289t2:c.3875T>C LRG_289p2:p.Phe1292Ser Q14524:p.Phe1293Ser - Protein change
- F1292S, F1293S, F1239S
- Other names
- -
- Canonical SPDI
- NC_000003.12:38562499:A:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00032
Exome Aggregation Consortium (ExAC) 0.00040
The Genome Aggregation Database (gnomAD) 0.00048
Trans-Omics for Precision Medicine (TOPMed) 0.00057
The Genome Aggregation Database (gnomAD), exomes 0.00065
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|---|---|---|---|---|
| Benign/Likely benign (7) |
criteria provided, multiple submitters, no conflicts
|
May 1, 2024 | RCV000058610.40 | |
| Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 7, 2024 | RCV000171772.18 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jul 23, 2014 | RCV000151781.12 | |
| Uncertain significance (1) |
no assertion criteria provided
|
Aug 1, 2016 | RCV000417329.10 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
- | RCV000845318.11 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV001147537.12 | |
| Likely benign (1) |
criteria provided, single submitter
|
Dec 17, 2019 | RCV001842352.10 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Mar 30, 2021 | RCV003224134.8 | |
| Likely benign (1) |
criteria provided, single submitter
|
Mar 13, 2018 | RCV002354250.9 |
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. |
|
|---|---|---|---|---|---|
|
Likely benign
(Jun 24, 2013)
|
criteria provided, single submitter
Method: research
|
Brugada syndrome
Affected status: unknown
Allele origin:
unknown
|
Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000055220.1 First in ClinVar: Jun 08, 2015 Last updated: Jun 08, 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
|
|
|
Uncertain significance
(Jul 23, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000200232.5
First in ClinVar: Jan 30, 2015 Last updated: Jan 30, 2015 |
Comment:
The Phe1293Ser variant in SCN5A has been reported in 2 individuals with Brugada syndrome (Priori 2002, Sommariva 2012), one of whom carried a frameshift variant … (more)
The Phe1293Ser variant in SCN5A has been reported in 2 individuals with Brugada syndrome (Priori 2002, Sommariva 2012), one of whom carried a frameshift variant in the other copy of SCN5A, but has also been identified in 1/590 Caucasian con trol chromosomes (Ackerman 2004) and in 4/8412 European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/; dbSNP rs41311 127). This variant has also been identified by our laboratory in 1 Caucasian ind ividual with DCM, who had a pathogenic variant in a different gene. The affected amino acid is poorly conserved in evolution, raising the possibility that a cha nge at this position would be tolerated. Other computational prediction tools do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the Phe1293Ser variant is uncertain. (less)
Number of individuals with the variant: 2
|
|
|
Uncertain significance
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Familial dilated cardiomyopathy
Affected status: yes
Allele origin:
germline
|
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
Accession: SCV000987360.1
First in ClinVar: Sep 08, 2019 Last updated: Sep 08, 2019 |
|
|
|
Likely benign
(Jul 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV001145505.1
First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020 |
|
|
|
Uncertain significance
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Brugada syndrome 1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001308366.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
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, … (more)
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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
|
|
|
Likely benign
(Dec 17, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Arrhythmia
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000904417.2
First in ClinVar: May 20, 2019 Last updated: Jun 22, 2020 |
|
|
|
Uncertain significance
(Mar 30, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Ventricular fibrillation, paroxysmal familial, type 1
Progressive familial heart block, type 1A Dilated cardiomyopathy 1E Progressive familial heart block, type 1A Long QT syndrome 3 Sick sinus syndrome 1 Brugada syndrome 1 Atrial fibrillation, familial, 10 SUDDEN INFANT DEATH SYNDROME
Affected status: unknown
Allele origin:
germline
|
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV003920441.1
First in ClinVar: Apr 30, 2023 Last updated: Apr 30, 2023 |
Comment:
SCN5A NM_198056.3 exon 22 p.Phe1293Ser (c.3878T>C): This variant has been reported in the literature in at least two individuals with Brugada syndrome, one of whom … (more)
SCN5A NM_198056.3 exon 22 p.Phe1293Ser (c.3878T>C): This variant has been reported in the literature in at least two individuals with Brugada syndrome, one of whom also carried a truncating variant in SCN5A (Priori 2002 PMID:11901046, Sommariva 2012). However, this variant is present in 0.9% (93/10336) of Ashkenazi Jewish alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/3-38603991-A-G) and is present in ClinVar, with several labs classifying this variant as likely benign (Variation ID:67833). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. (less)
|
|
|
Likely benign
(Jan 28, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000545025.8
First in ClinVar: Jun 08, 2015 Last updated: Feb 20, 2024 |
|
|
|
Likely benign
(Mar 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002620547.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely 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
(Feb 07, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Brugada syndrome
Affected status: yes
Allele origin:
germline
|
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals
Accession: SCV005382573.1
First in ClinVar: Nov 03, 2024 Last updated: Nov 03, 2024 |
|
|
|
Likely benign
(May 30, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000700035.1
First in ClinVar: Oct 09, 2016 Last updated: Oct 09, 2016 |
Comment:
Variant summary: The SCN5A c.3878T>C (p.Phe1293Ser) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant … (more)
Variant summary: The SCN5A c.3878T>C (p.Phe1293Ser) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 49/119844 control chromosomes including ExAC at a frequency of 0.0004089, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic SCN5A variant (0.0001667), suggesting this variant is likely a benign polymorphism. This variant has been reported in two Brugada syndrome (BrS) patients and one patient presenting with sodium channelopathy (cardiac symptoms, positive family history, and/or abnormal electrocardiogram) in literature (Priori_2002, Chockalingam_2012, and Sommariva_2013). In one BrS patient, another truncating variant c.3258-3261del4 (p.E1087PfsX57) was also present (Sommariva_2013), supporting benign outcome. It has been also reported as polymorphism from published sources (Kapa_2009, Kapplinger_2010) as it was found in healthy controls of European origin. In ClinVar while two clinical labs have classified this variant as VUS, one lab has classified as likely benign. Taken together, this variant is currently classified as likely benign. (less)
|
|
|
Benign
(Mar 03, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001863841.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 33083721, 30847666, 29167113, 27153395, 11901046, 22885917, 15851227, 20129283, 23414114)
|
|
|
Likely benign
(May 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001500310.23
First in ClinVar: Mar 14, 2021 Last updated: Oct 20, 2024 |
Comment:
SCN5A: BS2
Number of individuals with the variant: 20
|
|
|
Uncertain significance
(Aug 01, 2016)
|
no assertion criteria provided
Method: research
|
Long QT syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
CSER _CC_NCGL, University of Washington
Study: CSER - NEXT Medicine variant annotation
Accession: SCV000503533.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
Found in patient having exome sequencing for an unrelated indication. No known history of Long QT syndrome.
|
|
|
Uncertain significance
(Jan 17, 2017)
|
no assertion criteria provided
Method: provider interpretation
|
not provided
Affected status: unknown
Allele origin:
germline
|
Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000924950.1
First in ClinVar: Jun 29, 2019 Last updated: Jun 29, 2019 |
|
|
|
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: SCV000090130.3
First in ClinVar: Oct 22, 2013 Last updated: Oct 09, 2016 |
Comment:
This variant has been reported in the following publications (PMID:11901046;PMID:15851227;PMID:19841300;PMID:20129283).
|
|
| click to load more click to collapse | |||||
Comment:
Comment:
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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Comment:
SCN5A NM_198056.3 exon 22 p.Phe1293Ser (c.3878T>C): This variant has been reported in the literature in at least two individuals with Brugada syndrome, one of whom also carried a truncating variant in SCN5A (Priori 2002 PMID:11901046, Sommariva 2012). However, this variant is present in 0.9% (93/10336) of Ashkenazi Jewish alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/3-38603991-A-G) and is present in ClinVar, with several labs classifying this variant as likely benign (Variation ID:67833). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Comment:
This alteration is classified as likely 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.
Comment:
Variant summary: The SCN5A c.3878T>C (p.Phe1293Ser) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 49/119844 control chromosomes including ExAC at a frequency of 0.0004089, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic SCN5A variant (0.0001667), suggesting this variant is likely a benign polymorphism. This variant has been reported in two Brugada syndrome (BrS) patients and one patient presenting with sodium channelopathy (cardiac symptoms, positive family history, and/or abnormal electrocardiogram) in literature (Priori_2002, Chockalingam_2012, and Sommariva_2013). In one BrS patient, another truncating variant c.3258-3261del4 (p.E1087PfsX57) was also present (Sommariva_2013), supporting benign outcome. It has been also reported as polymorphism from published sources (Kapa_2009, Kapplinger_2010) as it was found in healthy controls of European origin. In ClinVar while two clinical labs have classified this variant as VUS, one lab has classified as likely benign. Taken together, this variant is currently classified as likely benign.
Comment:
This variant is associated with the following publications: (PMID: 33083721, 30847666, 29167113, 27153395, 11901046, 22885917, 15851227, 20129283, 23414114)
Comment:
SCN5A: BS2
Comment:
Found in patient having exome sequencing for an unrelated indication. No known history of Long QT syndrome.
Comment:
This variant has been reported in the following publications (PMID:11901046;PMID:15851227;PMID:19841300;PMID:20129283).
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:
The Phe1293Ser variant in SCN5A has been reported in 2 individuals with Brugada syndrome (Priori 2002, Sommariva 2012), one of whom carried a frameshift variant in the other copy of SCN5A, but has also been identified in 1/590 Caucasian con trol chromosomes (Ackerman 2004) and in 4/8412 European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/; dbSNP rs41311 127). This variant has also been identified by our laboratory in 1 Caucasian ind ividual with DCM, who had a pathogenic variant in a different gene. The affected amino acid is poorly conserved in evolution, raising the possibility that a cha nge at this position would be tolerated. Other computational prediction tools do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the Phe1293Ser variant is uncertain.
Comment:
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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Comment:
SCN5A NM_198056.3 exon 22 p.Phe1293Ser (c.3878T>C): This variant has been reported in the literature in at least two individuals with Brugada syndrome, one of whom also carried a truncating variant in SCN5A (Priori 2002 PMID:11901046, Sommariva 2012). However, this variant is present in 0.9% (93/10336) of Ashkenazi Jewish alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/3-38603991-A-G) and is present in ClinVar, with several labs classifying this variant as likely benign (Variation ID:67833). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Comment:
This alteration is classified as likely 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.
Comment:
Variant summary: The SCN5A c.3878T>C (p.Phe1293Ser) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 49/119844 control chromosomes including ExAC at a frequency of 0.0004089, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic SCN5A variant (0.0001667), suggesting this variant is likely a benign polymorphism. This variant has been reported in two Brugada syndrome (BrS) patients and one patient presenting with sodium channelopathy (cardiac symptoms, positive family history, and/or abnormal electrocardiogram) in literature (Priori_2002, Chockalingam_2012, and Sommariva_2013). In one BrS patient, another truncating variant c.3258-3261del4 (p.E1087PfsX57) was also present (Sommariva_2013), supporting benign outcome. It has been also reported as polymorphism from published sources (Kapa_2009, Kapplinger_2010) as it was found in healthy controls of European origin. In ClinVar while two clinical labs have classified this variant as VUS, one lab has classified as likely benign. Taken together, this variant is currently classified as likely benign.
Comment:
This variant is associated with the following publications: (PMID: 33083721, 30847666, 29167113, 27153395, 11901046, 22885917, 15851227, 20129283, 23414114)
Comment:
SCN5A: BS2
Comment:
Found in patient having exome sequencing for an unrelated indication. No known history of Long QT syndrome.
Comment:
This variant has been reported in the following publications (PMID:11901046;PMID:15851227;PMID:19841300;PMID:20129283).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| High prevalence of genetic variants previously associated with Brugada syndrome in new exome data. | Risgaard B | Clinical genetics | 2013 | PMID: 23414114 |
| Genetics can contribute to the prognosis of Brugada syndrome: a pilot model for risk stratification. | Sommariva E | European journal of human genetics : EJHG | 2013 | PMID: 23321620 |
| The diagnostic and therapeutic aspects of loss-of-function cardiac sodium channelopathies in children. | Chockalingam P | Heart rhythm | 2012 | PMID: 22885917 |
| Paralogous annotation of disease-causing variants in long QT syndrome genes. | Ware JS | Human mutation | 2012 | PMID: 22581653 |
| 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 |
| 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 |
| Natural history of Brugada syndrome: insights for risk stratification and management. | Priori SG | Circulation | 2002 | PMID: 11901046 |
Text-mined citations for rs41311127 ...
HelpThese 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
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.