ClinVar Miner

Submissions for variant NM_003978.5(PSTPIP1):c.748G>C (p.Glu250Gln)

dbSNP: rs28939089
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000004684 SCV004297660 pathogenic Pyogenic arthritis-pyoderma gangrenosum-acne syndrome 2023-08-31 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 250 of the PSTPIP1 protein (p.Glu250Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with PAPA syndrome (PMID: 11971877, 16527883, 20506269, 22161697). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4434). 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: 11971877). This variant disrupts the p.Glu250 amino acid residue in PSTPIP1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22161697, 22513199, 25845478, 26025129; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004684 SCV000024859 pathogenic Pyogenic arthritis-pyoderma gangrenosum-acne syndrome 2002-04-15 no assertion criteria provided literature only

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