Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Revvity Omics, |
RCV001785886 | SCV002021300 | likely pathogenic | Upshaw-Schulman syndrome | 2019-09-27 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003728006 | SCV004540482 | likely pathogenic | not provided | 2023-08-04 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 1323853). This missense change has been observed in individual(s) with congenital thrombotic thrombocytopenic purpura (PMID: 24859360, 29763513). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs201457594, gnomAD 0.009%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 498 of the ADAMTS13 protein (p.Arg498Cys). |