ClinVar Genomic variation as it relates to human health
NM_000459.5(TEK):c.2740C>T (p.Leu914Phe)
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_000459.5(TEK):c.2740C>T (p.Leu914Phe)
Variation ID: 981229 Accession: VCV000981229.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9p21.2 9: 27212760 (GRCh38) [ NCBI UCSC ] 9: 27212758 (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 Mar 18, 2021 Dec 24, 2023 Oct 17, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000459.5:c.2740C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000450.3:p.Leu914Phe missense NM_000459.3:c.2740C>T NM_001290077.2:c.2611C>T NP_001277006.2:p.Leu871Phe missense NM_001290078.2:c.2296C>T NP_001277007.2:p.Leu766Phe missense NM_001375475.1:c.2737C>T NP_001362404.1:p.Leu913Phe missense NM_001375476.1:c.2608C>T NP_001362405.1:p.Leu870Phe missense NC_000009.12:g.27212760C>T NC_000009.11:g.27212758C>T NG_011828.1:g.108612C>T NG_011828.2:g.108621C>T - Protein change
- L766F, L870F, L871F, L913F, L914F
- Other names
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- Canonical SPDI
- NC_000009.12:27212759:C:T
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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.
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- 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 | ||
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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
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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TEK | - | - |
GRCh38 GRCh37 |
338 | 422 |
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
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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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Pathogenic (1) |
no assertion criteria provided
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- | RCV001327973.2 | |
Pathogenic (1) |
no assertion criteria provided
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Jun 1, 2021 | RCV001799752.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 13, 2020 | RCV002254341.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 17, 2023 | RCV003458658.1 |
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. |
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Pathogenic
(Mar 13, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
somatic
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Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital
Accession: SCV002525610.1
First in ClinVar: Jun 11, 2022 Last updated: Jun 11, 2022 |
Comment:
This is the most common somatic variant reported in individuals with sporadically occurring venous malformations (PMID: 19079259, PMID: 23801934, PMID: 27519652, PMID: 21962923, PMID: 26637981).
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Venous malformation (present)
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Venous malformation (present)
Observation 3:
Number of individuals with the variant: 1
Clinical Features:
Vascular skin abnormality (present) , Hemihypertrophy of lower limb (present)
Observation 4:
Number of individuals with the variant: 1
Clinical Features:
Venous malformation (present)
Observation 5:
Number of individuals with the variant: 1
Clinical Features:
Venous malformation (present)
Observation 6:
Number of individuals with the variant: 1
Clinical Features:
Venous malformation (present)
Observation 7:
Number of individuals with the variant: 1
Observation 8:
Number of individuals with the variant: 1
Clinical Features:
Venous malformation (present)
Observation 9:
Number of individuals with the variant: 1
Clinical Features:
Vascular skin abnormality (present)
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Pathogenic
(Oct 17, 2023)
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criteria provided, single submitter
Method: clinical testing
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Vascular malformation
Affected status: yes
Allele origin:
somatic
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Clinical Genomics Laboratory, Washington University in St. Louis
Accession: SCV004176936.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
Comment:
The TEK c.2740C>T (p.Leu914Phe) variant was identified at an allelic fraction consistent with somatic origin. This variant has been identified in multiple individuals with sporadic … (more)
The TEK c.2740C>T (p.Leu914Phe) variant was identified at an allelic fraction consistent with somatic origin. This variant has been identified in multiple individuals with sporadic venous malformations (Limaye N et al., PMID: 19079259; Ye C et al., PMID: 21962923; Soblet J et al., PMID: 23801934; Limaye N et al., PMID: 26637981; Soblet J et al., PMID: 27519652). This variant has been reported in the ClinVar database as a pathogenic somatic variant by one submitter (ClinVar ID: 981229). This variant is absent from the general population (gnomAD v.3.1.2), indicating it is not a common variant. The TEK c.2740C>T (p.Leu914Phe) variant resides within the kinase domain of TIE2, an endothelium-specific receptor tyrosine kinase that is a critical functional domain (Shewchuk LM et al., PMID: 11080633). Computational predictors indicate that the variant is damaging, evidence that correlates with impact to TEK function. In support of this prediction, functional studies show that the TEK c.2740C>T (p.Leu914Phe) variant increases vascular tissue growth via constitutive TIE2 phosphorylation and induces aberrant vessel migration (Limaye N et al., PMID: 19079259; Uebelhoer M et al., PMID: 23633549; Nv§tynki M et al., PMID: 26319232; Cai Y et al., PMID: 31451744). Based on an internally developed protocol informed by the ACMG/AMP guidelines (Richards S et al., PMID: 25741868) and gene-specific practices from the ClinGen Criteria Specification Registry, the TEK c.2740C>T (p.Leu914Phe) variant is classified as pathogenic. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: provider interpretation
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Abnormal cardiovascular system morphology
Affected status: yes
Allele origin:
somatic
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MAGI's Lab - Research, MAGI Group
Accession: SCV001437649.1
First in ClinVar: Mar 18, 2021 Last updated: Mar 18, 2021 |
Observation 1: Observation 2: Observation 3: Observation 4: Observation 5: |
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Pathogenic
(Jun 01, 2021)
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no assertion criteria provided
Method: research
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Bockenheimer syndrome
Affected status: yes
Allele origin:
somatic
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Arin Greene Laboratory, Boston Children's Hospital, Harvard Medical School
Accession: SCV001739510.1
First in ClinVar: Jan 01, 2022 Last updated: Jan 01, 2022 |
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
venous malformation (present)
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
venous malformation (present)
Observation 3:
Number of individuals with the variant: 1
Clinical Features:
venous malformation (present)
Observation 4:
Number of individuals with the variant: 1
Clinical Features:
venous malformation (present)
Observation 5:
Number of individuals with the variant: 1
Clinical Features:
venous malformation (present)
Observation 6:
Number of individuals with the variant: 1
Clinical Features:
venous malformation (present)
Observation 7:
Number of individuals with the variant: 1
Clinical Features:
venous malformation (present)
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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
HelpThere 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 rs1825682849 ...
HelpRecord last updated Dec 30, 2023
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.