Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000757698 | SCV000886020 | uncertain significance | not provided | 2017-12-01 | criteria provided, single submitter | clinical testing | The PSTPIP1 c.1124C>T; p.Pro375Leu variant is not published in the medical literature, in gene-specific databases, or in the ClinVar database. The variant is not listed in the dbSNP variant database, nor in the general population-based databases (Exome Variant Server, Genome Aggregation Database). The proline at this position is weakly conserved across species and computational algorithms (AlignGVGD, PolyPhen2, SIFT) predict this variant is tolerated. However, this variant occurs in the SH3 domain, which is a critical functional domain for PSTPIP1 function. Considering available information, the clinical significance of this variant cannot be determined with certainty. Pathogenic PSTPIP1 variants are associated with Pyogenic sterile arthritis, pyoderma gangrenosum, and acne syndrome (PAPA, MIM# 604416). References: Marcos T et al. Proline-serine-threonine phosphatase interacting protein 1 inhibition of T-cell receptor signaling depends on its SH3 domain. FEBS J. 2014 Sep;281(17):3844-54. |
| Labcorp Genetics |
RCV001059189 | SCV001223804 | uncertain significance | Pyogenic arthritis-pyoderma gangrenosum-acne syndrome | 2019-04-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 375 of the PSTPIP1 protein (p.Pro375Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PSTPIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 618850). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |