Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001364541 | SCV001560695 | pathogenic | not provided | 2023-07-31 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.003%). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg169 amino acid residue in RUNX2. Other variant(s) that disrupt this residue have been observed in individuals with RUNX2-related conditions (PMID: 10545612, 12424590), 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 RUNX2 protein function. ClinVar contains an entry for this variant (Variation ID: 916703). This missense change has been observed in individuals with clinical features of cleidocranial dysplasia (PMID: 33987976; Invitae). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 169 of the RUNX2 protein (p.Arg169Trp). |
Ce |
RCV001364541 | SCV004163559 | likely pathogenic | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | RUNX2: PM2, PM5, PP3, PS4:Supporting |
Istanbul Faculty of Medicine, |
RCV001268934 | SCV001335540 | likely pathogenic | Cleidocranial dysostosis | 2020-05-23 | no assertion criteria provided | clinical testing | Segregates in family |