Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001046139 | SCV001210028 | likely pathogenic | not provided | 2023-02-22 | criteria provided, single submitter | clinical testing | 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 MATN3 protein function. This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 218 of the MATN3 protein (p.Tyr218Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of epiphyseal dysplasia (Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 843499). This variant disrupts the p.Tyr218 amino acid residue in MATN3. Other variant(s) that disrupt this residue have been observed in individuals with MATN3-related conditions (PMID: 16287128), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV001046139 | SCV001467997 | uncertain significance | not provided | 2020-08-06 | criteria provided, single submitter | clinical testing |