ClinVar Miner

Submissions for variant NM_003978.5(PSTPIP1):c.1207G>C (p.Gly403Arg) (rs369113632)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000999831 SCV000604948 uncertain significance Pyogenic arthritis-pyoderma gangrenosum-acne syndrome 2020-08-27 criteria provided, single submitter clinical testing The PSTPIP1 c.1207G>C;p.Gly403Arg variant (rs369113632) has been published in the literature in an individual with pyoderma gangrenosum (Zeeli 2015). The variant is reported in the ClinVar database (Variation ID: 440207) and in the general population with an overall allele frequency of 0.03% (77/246,962 alleles, including 1 homozygote) in the Genome Aggregation Database. The glycine at codon 403 is moderately conserved, but computational algorithms (PolyPhen2, SIFT) predict this variant is deleterious. Due to limited information, the clinical significance of the p.Gly403Arg variant is uncertain at this time. References: Zeeli T et al. Pyoderma gangrenosum, acne and ulcerative colitis in a patient with a novel mutation in the PSTPIP1 gene. Clin Exp Dermatol. 2015 40(4):367-72.
GeneDx RCV000507592 SCV000616836 uncertain significance not specified 2017-09-22 criteria provided, single submitter clinical testing 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.
Invitae RCV000999831 SCV000642077 benign Pyogenic arthritis-pyoderma gangrenosum-acne syndrome 2020-10-05 criteria provided, single submitter clinical testing

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