Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001931077 | SCV002191384 | uncertain significance | Pyogenic arthritis-pyoderma gangrenosum-acne syndrome | 2023-09-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 228 of the PSTPIP1 protein (p.Arg228Cys). This variant is present in population databases (rs781341816, gnomAD 0.006%). This missense change has been observed in individual(s) with primary immunodeficiencies or autoinflammatory syndromes (PMID: 24139496, 30783801). ClinVar contains an entry for this variant (Variation ID: 1418985). 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 PSTPIP1 protein function. Experimental studies have shown that this missense change affects PSTPIP1 function (PMID: 29432774, 35152348). 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. |