Submissions for variant NM_001114753.3(ENG):c.392C>T (p.Pro131Leu)

gnomAD frequency: 0.00077  dbSNP: rs139398993

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Hereditary Hemorrhagic Telangiectasia Variant Curation Expert Panel, ClinGen	RCV000346221	SCV004805876	benign	Telangiectasia, hereditary hemorrhagic, type 1	2024-03-15	reviewed by expert panel	curation	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).
CSER _CC_NCGL, University of Washington	RCV000148486	SCV000190189	uncertain significance	Haemorrhagic telangiectasia 1	2014-06-01	criteria provided, single submitter	research	Low GERP score may suggest that this variant may belong in a lower pathogenicity class
Eurofins Ntd Llc (ga)	RCV000178045	SCV000230031	benign	not specified	2015-02-06	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000346221	SCV000477348	benign	Telangiectasia, hereditary hemorrhagic, type 1	2018-03-06	criteria provided, single submitter	clinical testing	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.
Invitae	RCV000857942	SCV000557862	benign	Hereditary hemorrhagic telangiectasia	2024-01-29	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000178045	SCV000594548	likely benign	not specified	2016-08-18	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000346221	SCV001156616	benign	Telangiectasia, hereditary hemorrhagic, type 1	2023-11-01	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001258238	SCV001435144	benign	Galloway-Mowat syndrome 1		criteria provided, single submitter	research	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.
GeneDx	RCV001588996	SCV001823090	likely benign	not provided	2018-08-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 32560555, 28655553, 27535533, 27146957, 12673790, 15879500, 25637381, 23399955, 21158752, 24055113)
CeGaT Center for Human Genetics Tuebingen	RCV001588996	SCV002546087	benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	ENG: BP4, BS1, BS2
Ambry Genetics	RCV002371988	SCV002624242	benign	Cardiovascular phenotype	2015-09-04	criteria provided, single submitter	clinical testing	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.