Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001390635 | SCV001592433 | pathogenic | not provided | 2022-09-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly719 amino acid residue in COMP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11746044, 17394206). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 COMP protein function. ClinVar contains an entry for this variant (Variation ID: 40997). This missense change has been observed in individuals with clinical features of pseudoachondroplasia (PMID: 15756302, 21922596; Invitae). 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 719 of the COMP protein (p.Gly719Ser). |
| Gene |
RCV001390635 | SCV004021571 | likely pathogenic | not provided | 2023-07-18 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25525159, 21922596, 15756302) |
| Gene |
RCV000033889 | SCV000057797 | not provided | Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome | no assertion provided | literature only |