Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000231956 | SCV000291951 | likely pathogenic | not provided | 2014-03-27 | criteria provided, single submitter | clinical testing | The c.517_518delAG variant in the PSTPIP1 gene causes a frameshift starting with codon Glutamine 174, changes this amino acid to a Glutamic acid residue, and creates a premature Stop codon at position 30 of the new reading frame, denoted p.Gln174GlufsX30. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. However, to date, only missense mutations have been reported in the PSTPIP1 gene. Therefore, although this variant is a strong candidate for a pathogenic mutation, the possibility that it is a benign variant cannot be excluded. |
| Labcorp Genetics |
RCV003765462 | SCV004638766 | uncertain significance | Pyogenic arthritis-pyoderma gangrenosum-acne syndrome | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln174Glufs*30) in the PSTPIP1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in PSTPIP1 cause disease. This variant is present in population databases (rs745343304, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with PSTPIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 242302). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |