Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000649776 | SCV000771609 | uncertain significance | BAP1-related tumor predisposition syndrome | 2023-12-18 | 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 588 of the BAP1 protein (p.Pro588Arg). This variant is present in population databases (rs780338105, gnomAD 0.0009%). 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: 539906). 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. |
Gene |
RCV001775940 | SCV002013976 | uncertain significance | not provided | 2020-03-16 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function |
Color Diagnostics, |
RCV001805780 | SCV002053173 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-07 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with arginine at codon 588 of the BAP1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251338 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV001805780 | SCV003990597 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-07 | criteria provided, single submitter | clinical testing | The p.P588R variant (also known as c.1763C>G), located in coding exon 14 of the BAP1 gene, results from a C to G substitution at nucleotide position 1763. The proline at codon 588 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. |
Baylor Genetics | RCV000649776 | SCV004214889 | uncertain significance | BAP1-related tumor predisposition syndrome | 2023-06-19 | criteria provided, single submitter | clinical testing |