ClinVar Genomic variation as it relates to human health
NM_001165963.4(SCN1A):c.5864T>C (p.Ile1955Thr)
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_001165963.4(SCN1A):c.5864T>C (p.Ile1955Thr)
Variation ID: 93660 Accession: VCV000093660.30
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q24.3 2: 165991411 (GRCh38) [ NCBI UCSC ] 2: 166847921 (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 17, 2014 Apr 15, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001165963.4:c.5864T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001159435.1:p.Ile1955Thr missense NM_001165964.3:c.5780T>C NP_001159436.1:p.Ile1927Thr missense NM_001202435.3:c.5864T>C NP_001189364.1:p.Ile1955Thr missense NM_001353948.2:c.5864T>C NP_001340877.1:p.Ile1955Thr missense NM_001353949.2:c.5831T>C NP_001340878.1:p.Ile1944Thr missense NM_001353950.2:c.5831T>C NP_001340879.1:p.Ile1944Thr missense NM_001353951.2:c.5831T>C NP_001340880.1:p.Ile1944Thr missense NM_001353952.2:c.5831T>C NP_001340881.1:p.Ile1944Thr missense NM_001353954.2:c.5828T>C NP_001340883.1:p.Ile1943Thr missense NM_001353955.2:c.5828T>C NP_001340884.1:p.Ile1943Thr missense NM_001353957.2:c.5780T>C NP_001340886.1:p.Ile1927Thr missense NM_001353958.2:c.5780T>C NP_001340887.1:p.Ile1927Thr missense NM_001353960.2:c.5777T>C NP_001340889.1:p.Ile1926Thr missense NM_001353961.2:c.3422T>C NP_001340890.1:p.Ile1141Thr missense NM_006920.6:c.5831T>C NP_008851.3:p.Ile1944Thr missense NR_148667.2:n.6281T>C non-coding transcript variant NC_000002.12:g.165991411A>G NC_000002.11:g.166847921A>G NG_011906.1:g.87229T>C LRG_8:g.87229T>C P35498:p.Ile1955Thr - Protein change
- I1944T, I1955T, I1141T, I1927T, I1926T, I1943T
- Other names
- p.I1955T:ATA>ACA
- Canonical SPDI
- NC_000002.12:165991410:A:G
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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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0.00759 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00194
Exome Aggregation Consortium (ExAC) 0.00237
1000 Genomes Project 0.00759
The Genome Aggregation Database (gnomAD) 0.00876
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00930
1000 Genomes Project 30x 0.00937
Trans-Omics for Precision Medicine (TOPMed) 0.00954
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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SCN1A | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2175 | 4517 | |
LOC102724058 | - | - | - | GRCh38 | - | 2288 |
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, multiple submitters, no conflicts
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Aug 27, 2013 | RCV000079592.25 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Aug 1, 2023 | RCV000224940.16 | |
Likely benign (1) |
criteria provided, single submitter
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Jun 14, 2016 | RCV000344701.13 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV000395905.13 | |
Benign (1) |
criteria provided, single submitter
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Jan 31, 2024 | RCV001082156.15 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV001133025.12 | |
Benign (1) |
criteria provided, single submitter
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Apr 26, 2016 | RCV002311585.8 |
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
(Aug 27, 2013)
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criteria provided, single submitter
Method: clinical testing
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AllHighlyPenetrant
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000152609.1
First in ClinVar: May 17, 2014 Last updated: May 17, 2014 |
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Benign
(-)
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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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PreventionGenetics, part of Exact Sciences
Accession: SCV000307040.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Likely benign
(Jun 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Seizure Disorders
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000417763.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Benign
(Jul 09, 2013)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000111474.8
First in ClinVar: Jan 23, 2014 Last updated: Oct 02, 2016 |
Number of individuals with the variant: 3
Sex: mixed
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Generalized epilepsy with febrile seizures plus, type 2
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001292711.1
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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Migraine, familial hemiplegic, 3
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000417764.3
First in ClinVar: Dec 06, 2016 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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Benign
(Apr 26, 2016)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000846998.4
First in ClinVar: Nov 08, 2018 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: 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)
Number of individuals with the variant: 1
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Early infantile epileptic encephalopathy with suppression bursts
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000559705.9
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
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Likely Benign
(Sep 25, 2015)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000281556.1
First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016 |
Comment:
Converted during submission to Likely benign.
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Benign
(Jun 26, 2013)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000171481.12
First in ClinVar: Jun 23, 2014 Last updated: Oct 02, 2016 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Benign
(Aug 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: SCV004011226.6
First in ClinVar: Jul 16, 2023 Last updated: Apr 15, 2024 |
Comment:
SCN1A: BP4, BS1, BS2
Number of individuals with the variant: 4
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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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Generalised epilepsy with febrile seizures plus (GEFS(+)): molecular analysis in a restricted area. | Polizzi A | Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery | 2012 | PMID: 22011963 |
Polymorphisms of the SCN1A gene in children and adolescents with primary headache and idiopathic or cryptogenic epilepsy: is there a linkage? | Toldo I | The journal of headache and pain | 2011 | PMID: 21713554 |
Sodium channels SCN1A, SCN2A and SCN3A in familial autism. | Weiss LA | Molecular psychiatry | 2003 | PMID: 12610651 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SCN1A | - | - | - | - |
Text-mined citations for rs35735053 ...
HelpRecord last updated Apr 15, 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.