Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001989940 | SCV002233537 | likely pathogenic | Hereditary hemorrhagic telangiectasia | 2025-01-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 476 of the ENG protein (p.Gln476Leu). 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: 20414677; internal data). ClinVar contains an entry for this variant (Variation ID: 1450035). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |