Description
The G403R missense variant in the PSTPIP1 gene has been reported previously in association with PAC syndrome (Pyoderma gangrenosum, Acne, and Ulcerative colitis) (Zeeli et al., 2015), with limited evidence for pathogenicity. This variant is observed in 28/15704 (0.178%) alleles from individuals of South Asian background in the ExAC dataset (Lek et al., 2016). G403R is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position in the SH3 domain that is conserved across species,and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, the pathogenicity of missense changes in this region of the PSTPIP1 protein is unclear, as all currently known pathogenic variants associated with PAPA syndrome have been identified in exons 10 and 11. In summary, based on the currently available information, it is unclear whether this variant is pathogenic or a rare benign variant.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
