Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
NIHR Bioresource Rare Diseases, |
RCV001262076 | SCV001439461 | likely pathogenic | Telangiectasia, hereditary hemorrhagic, type 1 | 2018-01-01 | criteria provided, single submitter | research | PM2+PM1+PP4 |
Labcorp Genetics |
RCV001880033 | SCV002296869 | likely pathogenic | Hereditary hemorrhagic telangiectasia | 2024-08-15 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 299 of the ENG protein (p.Leu299Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of hereditary hemorrhagic telangiectasia (PMID: 32573726; Invitae). ClinVar contains an entry for this variant (Variation ID: 982483). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ENG protein function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |