ClinVar Genomic variation as it relates to human health
NM_001114753.3(ENG):c.392C>T (p.Pro131Leu)
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.392C>T (p.Pro131Leu)
Variation ID: 161232 Accession: VCV000161232.43
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9q34.11 9: 127826641 (GRCh38) [ NCBI UCSC ] 9: 130588920 (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 Dec 7, 2014 May 1, 2024 Mar 15, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001114753.3:c.392C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001108225.1:p.Pro131Leu missense NM_000118.4:c.392C>T NP_000109.1:p.Pro131Leu missense NM_001278138.2:c.-155C>T 5 prime UTR NM_001406715.1:c.392C>T NP_001393644.1:p.Pro131Leu missense NC_000009.12:g.127826641G>A NC_000009.11:g.130588920G>A NG_009551.1:g.33128C>T LRG_589:g.33128C>T LRG_589t1:c.392C>T LRG_589p1:p.Pro131Leu LRG_589t2:c.392C>T LRG_589p2:p.Pro131Leu - Protein change
- P131L
- Other names
- NM_001114753.3(ENG):c.392C>T
- p.Pro131Leu
- Canonical SPDI
- NC_000009.12:127826640: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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0.00978 (A)
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Allele frequency
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00077
Trans-Omics for Precision Medicine (TOPMed) 0.00104
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00154
1000 Genomes Project 30x 0.00921
1000 Genomes Project 0.00978
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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ENG | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1082 | 1584 |
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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Uncertain significance (1) |
criteria provided, single submitter
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Jun 1, 2014 | RCV000148486.3 | |
Benign (3) |
reviewed by expert panel
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Mar 15, 2024 | RCV000346221.17 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Aug 18, 2016 | RCV000178045.9 | |
Benign (1) |
criteria provided, single submitter
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Jan 29, 2024 | RCV000857942.9 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2024 | RCV001588996.15 | |
Benign (1) |
criteria provided, single submitter
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Sep 4, 2015 | RCV002371988.2 | |
Benign (1) |
criteria provided, single submitter
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- | RCV001258238.3 |
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
(Mar 15, 2024)
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reviewed by expert panel
Method: curation
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Telangiectasia, hereditary hemorrhagic, type 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen Hereditary Hemorrhagic Telangiectasia Variant Curation Expert Panel, ClinGen
Accession: SCV004805876.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
Comment:
The NM_001114753.3: c.392C>T variant in ENG is a missense variant predicted to cause substitution of proline by leucine at amino acid 131 (p.Pro131Leu). The filtering … (more)
The NM_001114753.3: c.392C>T variant in ENG is a missense variant predicted to cause substitution of proline by leucine at amino acid 131 (p.Pro131Leu). The filtering allele frequency (the lower threshold of the 95% CI of 762/30612) of the c.392C>T variant in ENG is 0.02343 for South Asian chromosomes by gnomAD v2.1.1, which is higher than the ClinGen Hereditary Hemorrhagic Telangiectasia Variant Curation Expert Panel threshold (>0.01) for BA1, and therefore meets this criterion (BA1). The computational predictor REVEL gives a score of 0.315, which is neither above nor below the thresholds predicting a damaging or benign impact on ENG function. In summary, this variant meets the criteria to be classified as benign for autosomal dominant hereditary hemorrhagic telangiectasia based on the ACMG/AMP criteria applied, as specified by the ClinGen Hereditary Hemorrhagic Telangiectasia Variant Curation Expert Panel: BA1 (specification version 1.0.0; 1/4/2024). (less)
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Uncertain significance
(Jun 01, 2014)
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criteria provided, single submitter
Method: research
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Haemorrhagic telangiectasia 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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CSER _CC_NCGL, University of Washington
Study: ESP 6500 variant annotation
Accession: SCV000190189.2 First in ClinVar: Dec 07, 2014 Last updated: Dec 07, 2014
Comment:
Variants classified for the Actionable exomic incidental findings in 6503 participants: challenges of variant classification manuscript
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Comment:
Low GERP score may suggest that this variant may belong in a lower pathogenicity class
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Likely benign
(Aug 18, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000594548.1
First in ClinVar: Jun 28, 2015 Last updated: Jun 28, 2015 |
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Benign
(Feb 06, 2015)
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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: SCV000230031.5
First in ClinVar: Jun 28, 2015 Last updated: May 03, 2018 |
Number of individuals with the variant: 3
Sex: mixed
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Benign
(Mar 06, 2018)
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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:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000477348.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Likely benign
(Aug 03, 2018)
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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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GeneDx
Accession: SCV001823090.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 32560555, 28655553, 27535533, 27146957, 12673790, 15879500, 25637381, 23399955, 21158752, 24055113)
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Benign
(Jan 29, 2024)
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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: SCV000557862.9
First in ClinVar: Dec 06, 2016 Last updated: Feb 20, 2024 |
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Benign
(Nov 01, 2023)
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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:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001156616.4
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
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Benign
(Mar 01, 2024)
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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: SCV002546087.10
First in ClinVar: Jul 09, 2022 Last updated: Apr 15, 2024 |
Comment:
ENG: BP4, BS1, BS2
Number of individuals with the variant: 21
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Benign
(Sep 04, 2015)
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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: SCV002624242.2
First in ClinVar: Nov 29, 2022 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
(-)
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criteria provided, single submitter
Method: research
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Galloway-Mowat syndrome 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001435144.1
First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020 |
Comment:
The heterozygous p.Pro131Leu variant in ENG has been identified in multiple individuals with haemorrhagic telangiectasia and individuals without haemorrhagic telangiectasia (PMID: 15879500, 21158752), and has … (more)
The heterozygous p.Pro131Leu variant in ENG has been identified in multiple individuals with haemorrhagic telangiectasia and individuals without haemorrhagic telangiectasia (PMID: 15879500, 21158752), and has been identified in >2% of South Asian chromosomes and 7 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal dominant haemorrhagic telangiectasia. (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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Actionable, pathogenic incidental findings in 1,000 participants' exomes. | Dorschner MO | American journal of human genetics | 2013 | PMID: 24055113 |
Prevalence of germline PTEN, BMPR1A, SMAD4, STK11, and ENG mutations in patients with moderate-load colorectal polyps. | Ngeow J | Gastroenterology | 2013 | PMID: 23399955 |
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 |
Hereditary haemorrhagic telangiectasia: current views on genetics and mechanisms of disease. | Abdalla SA | Journal of medical genetics | 2006 | PMID: 15879500 |
Characterization of 17 novel endoglin mutations associated with hereditary hemorrhagic telangiectasia. | Cymerman U | Human mutation | 2003 | PMID: 12673790 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ENG | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/007c246a-5626-4580-b6dc-c5817c428f04 | - | - | - | - |
Text-mined citations for rs139398993 ...
HelpRecord last updated May 01, 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.