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NM_001165963.4(SCN1A):c.4467del (p.Lys1491fs)
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.
(1) 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.
Likely pathogenic
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001165963.4(SCN1A):c.4467del (p.Lys1491fs)
Variation ID: 632977 Accession: VCV000632977.1
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 2q24.3 2: 165998047 (GRCh38) [ NCBI UCSC ] 2: 166854557 (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 Jun 2, 2019 Jun 2, 2019 Aug 2, 2018 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001165963.4:c.4467del MANESelect Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001159435.1:p.Lys1491fs frameshift NM_001165964.3:c.4383del NP_001159436.1:p.Lys1463fs frameshift NM_001202435.3:c.4467del NP_001189364.1:p.Lys1491fs frameshift NM_001353948.2:c.4467del NP_001340877.1:p.Lys1491fs frameshift NM_001353949.2:c.4434del NP_001340878.1:p.Lys1480fs frameshift NM_001353950.2:c.4434del NP_001340879.1:p.Lys1480fs frameshift NM_001353951.2:c.4434del NP_001340880.1:p.Lys1480fs frameshift NM_001353952.2:c.4434del NP_001340881.1:p.Lys1480fs frameshift NM_001353954.2:c.4431del NP_001340883.1:p.Lys1479fs frameshift NM_001353955.2:c.4431del NP_001340884.1:p.Lys1479fs frameshift NM_001353957.2:c.4383del NP_001340886.1:p.Lys1463fs frameshift NM_001353958.2:c.4383del NP_001340887.1:p.Lys1463fs frameshift NM_001353960.2:c.4380del NP_001340889.1:p.Lys1462fs frameshift NM_001353961.2:c.2025del NP_001340890.1:p.Lys677fs frameshift NM_006920.6:c.4434del NP_008851.3:p.Lys1480fs frameshift NR_148667.2:n.4884del non-coding transcript variant NC_000002.12:g.165998047del NC_000002.11:g.166854557del NG_011906.1:g.80593del LRG_8:g.80593del - Protein change
- K1479fs, K677fs, K1462fs, K1463fs, K1480fs, K1491fs
- Other names
- -
- Canonical SPDI
- NC_000002.12:165998046:C:
- 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.
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- Links
- dbSNP: rs1559118914
- VarSome
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation | Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases. | Related variants | ||
|---|---|---|---|---|---|---|
| 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. | |||
| SCN1A | Sufficient evidence for dosage pathogenicity | No evidence available | GRCh38 GRCh37 | 2186 | 4534 | |
| LOC102724058 | - | - | - | GRCh38 | - | 2294 |
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. |
|---|---|---|---|---|
| Autosomal dominant epilepsy | Likely pathogenic (1) | Aug 2, 2018 | RCV000780698.1 |
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 pathogenic (Aug 02, 2018) | (LabCorp Variant Classification Summary - May 2015) Method: clinical testing | Autosomal dominant epilepsy Affected status: unknown Allele origin: germline | Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000918182.1 | Comment: Variant summary: SCN1A c.4467delG (p.Lys1491ArgfsX10) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more) Variant summary: SCN1A c.4467delG (p.Lys1491ArgfsX10) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.5536_5539delAAAC, p.Lys1846fsX11; c.5674C>T, p.Arg1892X; c.5734C>T, p.Arg1912X). The variant was absent in 118626 control chromosomes (ExAC). To our knowledge, no occurrence of c.4467delG in individuals affected with Febrile Seizures and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. (less) |
Comment:
Variant summary: SCN1A c.4467delG (p.Lys1491ArgfsX10) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.5536_5539delAAAC, p.Lys1846fsX11; c.5674C>T, p.Arg1892X; c.5734C>T, p.Arg1912X). The variant was absent in 118626 control chromosomes (ExAC). To our knowledge, no occurrence of c.4467delG in individuals affected with Febrile Seizures and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
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:
Variant summary: SCN1A c.4467delG (p.Lys1491ArgfsX10) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.5536_5539delAAAC, p.Lys1846fsX11; c.5674C>T, p.Arg1892X; c.5734C>T, p.Arg1912X). The variant was absent in 118626 control chromosomes (ExAC). To our knowledge, no occurrence of c.4467delG in individuals affected with Febrile Seizures and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Citations for germline classification of this variant
Help
There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.
Text-mined citations for rs1559118914 ...
Help
These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.
Record last updated Apr 25, 2022
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