Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001036464 | SCV001199830 | uncertain significance | Pyogenic arthritis-pyoderma gangrenosum-acne syndrome | 2023-02-22 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 62 of the PSTPIP1 protein (p.Arg62Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 835558). 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. |
| ARUP Laboratories, |
RCV001036464 | SCV002050265 | uncertain significance | Pyogenic arthritis-pyoderma gangrenosum-acne syndrome | 2020-10-15 | criteria provided, single submitter | clinical testing | The PSTPIP1 c.184C>T; p.Arg62Trp variant (rs375063664), to our knowledge, is not reported in the medical literature but is reported in a symptomatic individual in the InFevers database (see link below). The variant listed in the ClinVar database (Variation ID: 835558) and is reported in the general population with an overall allele frequency of 0.003% (6/225,810 alleles) in the Genome Aggregation Database. The arginine at codon 62 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.27). Due to limited information, the clinical significance of the p.Arg62Trp variant is uncertain at this time. References: Link to InFevers database: https://infevers.umai-montpellier.fr/web/search.php?n=5 |