Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000816406 | SCV000956913 | uncertain significance | Pyogenic arthritis-pyoderma gangrenosum-acne syndrome | 2022-11-12 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 659405). This variant has not been reported in the literature in individuals affected with PSTPIP1-related conditions. This variant is present in population databases (rs777380464, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 223 of the PSTPIP1 protein (p.Arg223Gln). |
| Illumina Laboratory Services, |
RCV000816406 | SCV001278164 | uncertain significance | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Gene |
RCV001766717 | SCV001990142 | uncertain significance | not provided | 2019-05-23 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
| Genome Diagnostics Laboratory, |
RCV002264012 | SCV002542893 | uncertain significance | Autoinflammatory syndrome | 2017-11-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004028887 | SCV005012949 | uncertain significance | Inborn genetic diseases | 2024-01-09 | criteria provided, single submitter | clinical testing | The c.668G>A (p.R223Q) alteration is located in exon 10 (coding exon 10) of the PSTPIP1 gene. This alteration results from a G to A substitution at nucleotide position 668, causing the arginine (R) at amino acid position 223 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |