Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000640443 | SCV000762034 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2023-03-26 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly309 amino acid residue in ACVRL1. Other variant(s) that disrupt this residue have been observed in individuals with ACVRL1-related conditions (PMID: 16705692, 21132305), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 533349). This missense change has been observed in individuals with hereditary haemorrhagic telangiectasia (PMID: 15517393, 17384219, 21158752, 22991266, 26245826). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 309 of the ACVRL1 protein (p.Gly309Ser). |
Mayo Clinic Laboratories, |
RCV004791659 | SCV005414081 | likely pathogenic | not provided | 2024-09-06 | criteria provided, single submitter | clinical testing | PP3, PM2, PM5, PS4_moderate |