Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001203720 | SCV001374896 | pathogenic | Hereditary hemorrhagic telangiectasia | 2020-10-12 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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.Leu572*) have been determined to be pathogenic (PMID: 11440987, 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 several individuals affected with hereditary hemorrhagic telangiectasia (HHT) (PMID: 16752392, 22991266, Invitae). This variant is also described as c.1698delG (p.R566fsX572 or p.Arg566fs) in the literature This sequence change results in a premature translational stop signal in the ENG gene (p.Thr567Leufs*6). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 59 amino acids of the ENG protein. |
Ambry Genetics | RCV002402581 | SCV002712434 | pathogenic | Cardiovascular phenotype | 2022-02-01 | criteria provided, single submitter | clinical testing | The c.1698delG pathogenic mutation, located in coding exon 13 of the ENG gene, results from a deletion of one nucleotide at nucleotide position 1698, causing a translational frameshift with a predicted alternate stop codon (p.T567Lfs*6). This alteration has been reported in individuals with hereditary hemorrhagic telangiectasia (HHT) (Bossler AD et al. Hum Mutat, 2006 Jul;27:667-75; Nishida T et al. Am J Med Genet A, 2012 Nov;158A:2829-34). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, 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. |