Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001233754 | SCV001406363 | pathogenic | Hereditary hemorrhagic telangiectasia | 2019-10-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the ENG protein. Other variant(s) that disrupt this region (p.Gln562*) have been determined to be pathogenic (PMID: 15517393, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has been observed in an individual affected with hereditary hemorrhagic telangiectasia (PMID: 16752392). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the ENG gene (p.Lys543Glnfs*24). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 83 amino acids of the ENG protein. |
| Ambry Genetics | RCV002402730 | SCV002706060 | pathogenic | Cardiovascular phenotype | 2018-04-02 | criteria provided, single submitter | clinical testing | The c.1626dupC pathogenic mutation, located in coding exon 12 of the ENG gene, results from a duplication of C at nucleotide position 1626, causing a translational frameshift with a predicted alternate stop codon (p.K543Qfs*24). This mutation, designated as 1627_1628dupC, was identified in an individual with epistaxis and telangiectasias (Bossler AD et al. Hum. Mutat., 2006 Jul;27:667-75). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |