ClinVar Miner

Submissions for variant NM_003978.5(PSTPIP1):c.1151A>G (p.Asp384Gly) (rs200771233)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000232064 SCV000291954 uncertain significance not specified 2017-02-10 criteria provided, single submitter clinical testing To our knowledge, the D384G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant. The D384G variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). It 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 within 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 the coiled-coil domain region. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000335704 SCV000394019 benign Pyogenic arthritis-pyoderma gangrenosum-acne syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV000335704 SCV000642076 benign Pyogenic arthritis-pyoderma gangrenosum-acne syndrome 2020-11-20 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000757701 SCV000886023 likely benign not provided 2018-06-11 criteria provided, single submitter clinical testing The PSTPIP1 c.1151A>G: p.Asp384Gly variant (rs200771233), to our knowledge, is not reported in the medical literature or in gene-specific databases. The variant is listed in the ClinVar database (Variation ID: 242305) and in the Genome Aggregation Database in 0.7% (221/30776 alleles, 2 homozygotes) of the South Asian population. The aspartic acid at this position is weakly conserved but computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Considering the increased allele frequency and the presence of homozygotes, this variant is considered likely benign.

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