Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000704218 | SCV000833157 | uncertain significance | BAP1-related tumor predisposition syndrome | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 598 of the BAP1 protein (p.Pro598Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 580624). 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 not expected to disrupt BAP1 protein function with a negative predictive value of 80%. 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. |
| Mendelics | RCV000704218 | SCV000838034 | uncertain significance | BAP1-related tumor predisposition syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001759410 | SCV002005347 | uncertain significance | not provided | 2019-04-19 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002397472 | SCV002714517 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-12 | criteria provided, single submitter | clinical testing | The p.P598R variant (also known as c.1793C>G), located in coding exon 14 of the BAP1 gene, results from a C to G substitution at nucleotide position 1793. The proline at codon 598 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |