ClinVar Genomic variation as it relates to human health
NM_001114753.3(ENG):c.808C>T (p.Gln270Ter)
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_001114753.3(ENG):c.808C>T (p.Gln270Ter)
Variation ID: 458355 Accession: VCV000458355.17
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9q34.11 9: 127825239 (GRCh38) [ NCBI UCSC ] 9: 130587518 (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 26, 2018 Feb 20, 2024 Jun 24, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001114753.3:c.808C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001108225.1:p.Gln270Ter nonsense NM_000118.4:c.808C>T NP_000109.1:p.Gln270Ter nonsense NM_001278138.2:c.262C>T NP_001265067.1:p.Gln88Ter nonsense NM_001406715.1:c.808C>T NP_001393644.1:p.Gln270Ter nonsense NC_000009.12:g.127825239G>A NC_000009.11:g.130587518G>A NG_009551.1:g.34530C>T LRG_589:g.34530C>T LRG_589t1:c.808C>T LRG_589p1:p.Gln270Ter LRG_589t2:c.808C>T LRG_589p2:p.Gln270Ter - Protein change
- Q270*, Q88*
- Other names
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- Canonical SPDI
- NC_000009.12:127825238: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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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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ENG | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1075 | 1576 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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
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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 (3) |
criteria provided, multiple submitters, no conflicts
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Jun 24, 2022 | RCV000525562.6 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 19, 2018 | RCV000757216.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 26, 2017 | RCV002231035.6 |
Submissions - Germline
Classification
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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
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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
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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
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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
(Jan 19, 2018)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000885360.1
First in ClinVar: Feb 18, 2019 Last updated: Feb 18, 2019 |
Comment:
The ENG c.808C>T; p.Gln270Ter variant is reported in the literature in a family affected with HHT (Torring 2014). This variant is also reported as pathogenic … (more)
The ENG c.808C>T; p.Gln270Ter variant is reported in the literature in a family affected with HHT (Torring 2014). This variant is also reported as pathogenic in ClinVar (Variation ID: 458355), and is absent from general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database). This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA that is subject to nonsense medicated decay. Based on the above information, this variant is considered pathogenic. REFERENCES Torring PM et al. National mutation study among Danish patients with hereditary haemorrhagic telangiectasia. Clin Genet. 2014 Aug;86(2):123-33. (less)
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Pathogenic
(Dec 20, 2020)
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criteria provided, single submitter
Method: clinical testing
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Telangiectasia, hereditary hemorrhagic, type 1
Affected status: yes
Allele origin:
germline
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Beijing Key Laboratry for Genetics of Birth Defects, Beijing Children's Hospital
Accession: SCV001499941.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Number of individuals with the variant: 1
Age: 0-9 years
Sex: female
Ethnicity/Population group: East Asia
Geographic origin: China
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Pathogenic
(Jun 24, 2022)
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criteria provided, single submitter
Method: clinical testing
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Telangiectasia, hereditary hemorrhagic, type 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002766788.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Dominant negative and loss of function are … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene and are associated with hereditary haemorrhagic telangiectasia type 1 (HHT; MIM#187300). Multiple pathogenic null variants have been reported, and missense variants have been demonstrated to have both loss of function and dominant negative effects on protein activity (PMIDs: 25080347, 25312062). (I). 0107 - This gene is associated with autosomal dominant disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other null variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. There are multiple likely pathogenic and pathogenic NMD-predicted variants that have been reported (DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in at least five individuals or families with hereditary haemorrhagic telangiectasia (ClinVar, PMIDs: 24001356, 29483005, 31455059). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
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Pathogenic
(Mar 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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Telangiectasia, hereditary hemorrhagic, type 1
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002797688.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Dec 26, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hereditary hemorrhagic telangiectasia
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000629580.5
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln270*) in the ENG gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln270*) in the ENG gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with hemorrhagic telangiectasia in a family (PMID: 24001356). Loss-of-function variants in ENG are known to be pathogenic (PMID: 21158752, 12673790). For these reasons, this variant has been classified as Pathogenic. (less)
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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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Current Status of Clinical Diagnosis and Genetic Analysis of Hereditary Hemorrhagic Telangiectasia in South Korea: Multicenter Case Series and a Systematic Review. | Kim D | Neurointervention | 2019 | PMID: 31455059 |
Clinical presentation and treatment paradigms of brain arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia. | Gamboa NT | Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia | 2018 | PMID: 29483005 |
Functional analysis of endoglin mutations from hereditary hemorrhagic telangiectasia type 1 patients reveals different mechanisms for endoglin loss of function. | Mallet C | Human molecular genetics | 2015 | PMID: 25312062 |
Investigation of endoglin wild-type and missense mutant protein heterodimerisation using fluorescence microscopy based IF, BiFC and FRET analyses. | Förg T | PloS one | 2014 | PMID: 25080347 |
National mutation study among Danish patients with hereditary haemorrhagic telangiectasia. | Tørring PM | Clinical genetics | 2014 | PMID: 24001356 |
Molecular diagnosis in hereditary hemorrhagic telangiectasia: findings in a series tested simultaneously by sequencing and deletion/duplication analysis. | McDonald J | Clinical genetics | 2011 | PMID: 21158752 |
Characterization of 17 novel endoglin mutations associated with hereditary hemorrhagic telangiectasia. | Cymerman U | Human mutation | 2003 | PMID: 12673790 |
Text-mined citations for rs1554810215 ...
HelpRecord last updated Feb 28, 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.