Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001041801 | SCV001205441 | pathogenic | Hereditary hemorrhagic telangiectasia | 2023-11-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu563Aspfs*12) in the ENG gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 63 amino acid(s) of the ENG protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of hereditary hemorrhagic telangiectasia (PMID: 10625079; Invitae). This variant is also known as "deltaAGTCCATAGGA, FS at 1689". ClinVar contains an entry for this variant (Variation ID: 839929). This variant disrupts a region of the ENG protein in which other variant(s) (p.Leu572) have been determined to be pathogenic (PMID: 11440987). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| ARUP Laboratories, |
RCV001286214 | SCV001472746 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 1 | 2020-02-25 | criteria provided, single submitter | clinical testing | The ENG c.1689_1699del; p.Glu563fs variant is reported in the literature in one individual with a clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT) and a reduced endoglin level in activated monocytes (Cymerman 2000). In testing performed at ARUP Laboratories, this variant has also been observed in two brothers with symptoms of HHT. This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting 11 nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on the available information, this variant is considered to be pathogenic. References: Cymerman et al. Identification of hereditary hemorrhagic telangiectasia type 1 in newborns by protein expression and mutation analysis of endoglin. Pediatr Res. 2000 Jan;47(1):24-35. |
| Mayo Clinic Laboratories, |
RCV003480915 | SCV004226799 | pathogenic | not provided | 2022-06-20 | criteria provided, single submitter | clinical testing | PM2_supporting, PS4_moderate, PVS1 |