Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002233257 | SCV000822351 | pathogenic | Hereditary hemorrhagic telangiectasia | 2021-04-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ENG are known to be pathogenic (PMID: 15879500, 20656886, 22385575). This variant has been observed in several individuals affected with hereditary hemorrhagic telangiectasia (PMID: 12673790, 15024723, 15517393, 22991266). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser449Phefs*51) in the ENG gene. It is expected to result in an absent or disrupted protein product. |
Mayo Clinic Laboratories, |
RCV001507759 | SCV001713505 | pathogenic | not provided | 2019-09-23 | criteria provided, single submitter | clinical testing | PVS1, PM2, PS4_Moderate, PP4 |
Gene |
RCV001507759 | SCV002538893 | pathogenic | not provided | 2022-06-20 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 22991266, 15879500, 23801935, 15880681, 15517393, 15024723, 32300199, 12673790, 15907823, 16470787) |
Ambry Genetics | RCV002386207 | SCV002693309 | pathogenic | Cardiovascular phenotype | 2019-05-08 | criteria provided, single submitter | clinical testing | The c.1346_1347delCT pathogenic mutation, located in coding exon 11 of the ENG gene, results from a deletion of two nucleotides at nucleotide positions 1346 to 1347, causing a translational frameshift with a predicted alternate stop codon (p.S449Ffs*51). This mutation was first described in a hereditary hemorrhagic telangiectasia (HHT) family with multiple affected individuals; the proband had reduced levels of endoglin compared to controls (Cymerman U et al. Hum. Mutat., 2003 May;21:482-92). This mutation has also been described in French, Dutch, and German individuals with HHT (Lesca G et al. Hum. Mutat., 2004 Apr;23:289-99; Letteboer TG et al. Hum. Genet., 2005 Jan;116:8-16; Schulte C et al. Hum. Mutat., 2005 Jun;25:595). 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. |