ClinVar Genomic variation as it relates to human health
NM_000335.5(SCN5A):c.1017C>T (p.Tyr339=)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000335.5(SCN5A):c.1017C>T (p.Tyr339=)
Variation ID: 227057 Accession: VCV000227057.40
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p22.2 3: 38606792 (GRCh38) [ NCBI UCSC ] 3: 38648283 (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 May 29, 2016 Oct 8, 2024 Feb 5, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000335.5:c.1017C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000326.2:p.Tyr339= synonymous NM_001099404.2:c.1017C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001092874.1:p.Tyr339= synonymous NM_001099404.1:c.1017C>T NM_001099405.2:c.1017C>T NP_001092875.1:p.Tyr339= synonymous NM_001160160.2:c.1017C>T NP_001153632.1:p.Tyr339= synonymous NM_001160161.2:c.1017C>T NP_001153633.1:p.Tyr339= synonymous NM_001354701.2:c.1017C>T NP_001341630.1:p.Tyr339= synonymous NM_198056.3:c.1017C>T NP_932173.1:p.Tyr339= synonymous NC_000003.12:g.38606792G>A NC_000003.11:g.38648283G>A NG_008934.1:g.47881C>T LRG_289:g.47881C>T LRG_289t1:c.1017C>T LRG_289p1:p.Tyr339= LRG_289t3:c.1017C>T - Protein change
- Other names
- -
- Canonical SPDI
- NC_000003.12:38606791: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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0.00479 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00090
Exome Aggregation Consortium (ExAC) 0.00098
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00320
The Genome Aggregation Database (gnomAD) 0.00354
Trans-Omics for Precision Medicine (TOPMed) 0.00411
1000 Genomes Project 0.00479
1000 Genomes Project 30x 0.00593
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
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. |
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SCN5A | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3779 | 4220 |
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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Benign (4) |
criteria provided, single submitter
|
Mar 19, 2012 | RCV000218397.15 | |
Benign (1) |
criteria provided, single submitter
|
Jul 6, 2016 | RCV000246135.12 | |
Benign (7) |
criteria provided, multiple submitters, no conflicts
|
Jan 31, 2024 | RCV000713128.27 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 5, 2024 | RCV001842967.12 | |
SCN5A-related disorder
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Benign (1) |
no assertion criteria provided
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May 3, 2019 | RCV004541319.2 |
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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Benign
(Feb 02, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000843699.1
First in ClinVar: Oct 20, 2018 Last updated: Oct 20, 2018 |
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Benign
(Oct 18, 2018)
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criteria provided, single submitter
Method: clinical testing
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Arrhythmia
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000913805.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
|
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Benign
(Mar 19, 2012)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000269795.3
First in ClinVar: May 29, 2016 Last updated: May 29, 2016 |
Comment:
p.Tyr339Tyr in Exon 09 of SCN5A: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, … (more)
p.Tyr339Tyr in Exon 09 of SCN5A: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence and has been identified in 0.9% (32/3422) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs17215493). (less)
Number of individuals with the variant: 3
|
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Benign
(Mar 03, 2015)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001846626.1
First in ClinVar: Sep 10, 2021 Last updated: Sep 10, 2021 |
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Benign
(Jan 31, 2024)
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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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000557148.8
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
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Benign
(Jul 06, 2016)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000317876.7
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)
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Benign
(Feb 05, 2024)
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criteria provided, single submitter
Method: clinical testing
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Cardiac arrhythmia
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004823195.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Number of individuals with the variant: 229
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Benign
(-)
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criteria provided, single submitter
Method: not provided
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not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005238216.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
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Benign
(May 01, 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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004011460.11
First in ClinVar: Jul 16, 2023 Last updated: Oct 08, 2024 |
Comment:
SCN5A: BP4, BP7, BS1, BS2
Number of individuals with the variant: 1
|
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001978009.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001978559.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001979062.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001979512.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001980542.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Benign
(May 03, 2019)
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no assertion criteria provided
Method: clinical testing
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SCN5A-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004790909.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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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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Rapid, sensitive and inexpensive detection of SCN5A genetic variations by high resolution melting analysis. | Millat G | Clinical biochemistry | 2009 | PMID: 19026623 |
Sodium channel abnormalities are infrequent in patients with long QT syndrome: identification of two novel SCN5A mutations. | Wattanasirichaigoon D | American journal of medical genetics | 1999 | PMID: 10508990 |
Text-mined citations for rs17215493 ...
HelpRecord last updated Oct 13, 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.