Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001225623 | SCV001397907 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 327 of the ACVRL1 protein (p.Ala327Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of hereditary hemorrhagic telangiectasia (Invitae). ClinVar contains an entry for this variant (Variation ID: 953343). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACVRL1 protein function. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV001751437 | SCV001996641 | uncertain significance | not provided | 2019-10-31 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect |
ARUP Laboratories, |
RCV001225623 | SCV002047817 | uncertain significance | Telangiectasia, hereditary hemorrhagic, type 2 | 2020-12-17 | criteria provided, single submitter | clinical testing | The ACVRL1 c.979G>C; p.Ala327Pro variant, to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 953343). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The alanine at codon 327 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.894). However, given the lack of clinical and functional data, the significance of the p.Ala327Pro variant is uncertain at this time. |