Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003062241 | SCV003441472 | uncertain significance | not provided | 2024-04-29 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 235 of the ADAMTS13 protein (p.Asp235Tyr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with thrombotic thrombocytopenic purpura (PMID: 23346910, 26342041, 29554699). ClinVar contains an entry for this variant (Variation ID: 2136831). 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 ADAMTS13 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ADAMTS13 function (PMID: 26342041, 29554699, 32365113). This variant disrupts the p.Asp235 amino acid residue in ADAMTS13. Other variant(s) that disrupt this residue have been observed in individuals with ADAMTS13-related conditions (PMID: 12753286), which suggests that this may be a clinically significant amino acid residue. 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. |
| Fulgent Genetics, |
RCV005045191 | SCV005681475 | likely pathogenic | Upshaw-Schulman syndrome | 2024-06-11 | criteria provided, single submitter | clinical testing |