ClinVar Miner

Submissions for variant NM_003978.5(PSTPIP1):c.82C>T (p.Arg28Trp) (rs767330325)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000233989 SCV000291949 uncertain significance not provided 2014-08-11 criteria provided, single submitter clinical testing To our knowledge, the R28W variant has neither been published as a mutation, nor reported as a benign polymorphism. It was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R28W variant 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 that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, this substitution does not occur in the coiled-coil domain region, the region where definitive PSTPIP1 mutations have been identified to date. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Invitae RCV001062059 SCV001226831 uncertain significance Pyogenic arthritis-pyoderma gangrenosum-acne syndrome 2019-03-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 28 of the PSTPIP1 protein (p.Arg28Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs767330325, ExAC 0.01%). This variant has not been reported in the literature in individuals with PSTPIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 242300). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). 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.

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