Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003555993 | SCV004297280 | pathogenic | not provided | 2023-03-03 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys348 amino acid residue in COMP. Other variant(s) that disrupt this residue have been observed in individuals with COMP-related conditions (PMID: 21922596, 24595329), 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 COMP protein function. ClinVar contains an entry for this variant (Variation ID: 9195). This missense change has been observed in individual(s) with pseudoachondroplasia (PMID: 11746045). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 348 of the COMP protein (p.Cys348Arg). |
| OMIM | RCV000009773 | SCV000029994 | pathogenic | Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome | 2001-11-22 | no assertion criteria provided | literature only |