Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000792733 | SCV000932046 | likely pathogenic | Hereditary hemorrhagic telangiectasia | 2024-10-31 | criteria provided, single submitter | clinical testing | This variant, c.1166_1168del, results in the deletion of 1 amino acid(s) of the ENG protein (p.Phe389del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with hereditary hemorrhagic telangiectasia (PMID: 15521985, 20414677, 21158752, 24603890, 32573726; internal data). This variant is also known as c.1165-1167delTTC. ClinVar contains an entry for this variant (Variation ID: 639827). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| NIHR Bioresource Rare Diseases, |
RCV001262050 | SCV001439430 | likely pathogenic | Telangiectasia, hereditary hemorrhagic, type 1 | 2018-01-01 | criteria provided, single submitter | research | PVS1+PM2+PP4 |
| Ambry Genetics | RCV002332587 | SCV002627213 | pathogenic | Cardiovascular phenotype | 2021-08-23 | criteria provided, single submitter | clinical testing | The c.1166_1168delTCT pathogenic mutation (also known as p.F389del) is located in coding exon 9 of the ENG gene. This variant results from an in-frame TCT deletion at nucleotide positions 1166 to 1168. This results in the in-frame deletion of a phenylalanine at codon 389. This deletion has been detected in multiple individuals with a clinical diagnosis or suspicion of hereditary hemorrhagic telangiectasia (Brusgaard K et al. Clin Genet, 2004 Dec;66:556-61; Richards-Yutz J et al. Hum Genet, 2010 Jul;128:61-77; McDonald J et al. Clin Genet, 2011 Apr;79:335-44; Tørring PM et al. PLoS One, 2014 Mar;9:e90272; Ambry internal data). Based on internal structural assessment, this alteration results in disruption of the structure of ZP domain of ENG (Bokhove M et al. Proc Natl Acad Sci U S A. 2016 Feb;113(6):1552-7). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |