Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genomic Medicine Center of Excellence, |
RCV000171246 | SCV000221443 | likely pathogenic | not provided | criteria provided, single submitter | research | ||
Labcorp Genetics |
RCV000171246 | SCV003441837 | uncertain significance | not provided | 2022-08-19 | criteria provided, single submitter | clinical testing | This missense change has been observed in individuals with multicentric osteolysis (PMID: 24637309, 29620724). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 180 of the MMP2 protein (p.Asp180Asn). ClinVar contains an entry for this variant (Variation ID: 191067). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Asp180 amino acid residue in MMP2. Other variant(s) that disrupt this residue have been observed in individuals with MMP2-related conditions (PMID: 22876575), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). |