Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000649795 | SCV000771629 | uncertain significance | BAP1-related tumor predisposition syndrome | 2023-12-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 393 of the BAP1 protein (p.Gln393Arg). 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: 539918). 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. |
Ambry Genetics | RCV001010150 | SCV001170304 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-22 | criteria provided, single submitter | clinical testing | The p.Q393R variant (also known as c.1178A>G), located in coding exon 12 of the BAP1 gene, results from an A to G substitution at nucleotide position 1178. The glutamine at codon 393 is replaced by arginine, an amino acid with highly similar properties. 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, |
RCV001010150 | SCV001341654 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-16 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with arginine at codon 393 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 been reported in an individual affected with renal clear cell carcinoma in the TCGA database (KIRC_5707-11A). This variant has been identified in 1/248316 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. |