Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000566488 | SCV000672755 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-27 | criteria provided, single submitter | clinical testing | The p.R518Q variant (also known as c.1553G>A), located in coding exon 13 of the BAP1 gene, results from a G to A substitution at nucleotide position 1553. The arginine at codon 518 is replaced by glutamine, an amino acid with highly similar properties. This alteration was observed in a cohort of 192 BRCA negative high-risk HBOC families who under went multi-gene panel testing (Bonache S et al. J Cancer Res Clin Oncol, 2018 Dec;144:2495-2513). This amino acid position is highly conserved in available vertebrate species. 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. |
Color Diagnostics, |
RCV000566488 | SCV000687938 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-19 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000815049 | SCV000955491 | uncertain significance | BAP1-related tumor predisposition syndrome | 2024-01-06 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 518 of the BAP1 protein (p.Arg518Gln). This variant is present in population databases (rs535796204, gnomAD 0.007%). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 30306255). ClinVar contains an entry for this variant (Variation ID: 485247). 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. |
Baylor Genetics | RCV000815049 | SCV004213216 | uncertain significance | BAP1-related tumor predisposition syndrome | 2023-09-14 | criteria provided, single submitter | clinical testing |