Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000701307 | SCV000830101 | pathogenic | Hereditary hemorrhagic telangiectasia | 2021-09-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg478Serfs*22) in the ENG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ENG are known to be pathogenic (PMID: 15879500). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 9554745, 15880681). This variant is not present in population databases (ExAC no frequency). |
ARUP Laboratories, |
RCV001803945 | SCV002049112 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 1 | 2021-01-05 | criteria provided, single submitter | clinical testing | The ENG c.1434_1435delAG; p.Arg478SerfsTer22 variant (rs1564452747), also known as c.1432-1433delAG, is reported in the literature in multiple individuals affected with HHT (Gallione 1998, Schulte 2005). This variant is reported in ClinVar (Variation ID: 578331), and is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by deleting 2 nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Gallione CJ et al. Mutation and expression analysis of the endoglin gene in hereditary hemorrhagic telangiectasia reveals null alleles. Hum Mutat. 1998;11(4):286-94. PMID: 9554745. Schulte C et al. High frequency of ENG and ALK1/ACVRL1 mutations in German HHT patients. Hum Mutat. 2005 Jun;25(6):595. PMID: 15880681. |
Ce |
RCV002275142 | SCV002564068 | pathogenic | not provided | 2022-12-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002388311 | SCV002699262 | pathogenic | Cardiovascular phenotype | 2020-03-20 | criteria provided, single submitter | clinical testing | The c.1434_1435delAG pathogenic mutation, located in coding exon 12 of the ENG gene, results from a deletion of two nucleotides between nucleotide positions 1434 and 1435, causing a translational frameshift with a predicted alternate stop codon. This pathogenic mutation has been seen in multiple individuals with a diagnosis of hereditary hemorrhagic telangiectasia in both Dutch and German populations (Gallione CJ et al. Hum. Mutat. 1998; 11:286-94, Schulte C et al. Hum. Mutat. 2005; 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. |
Mayo Clinic Laboratories, |
RCV002275142 | SCV004226801 | pathogenic | not provided | 2022-10-11 | criteria provided, single submitter | clinical testing | PM2_supporting, PS4_moderate, PVS1 |