Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000649769 | SCV000771601 | uncertain significance | BAP1-related tumor predisposition syndrome | 2023-02-12 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 539899). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 708 of the BAP1 protein (p.Arg708Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with BAP1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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 | RCV002422384 | SCV002729925 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-29 | criteria provided, single submitter | clinical testing | The p.R708W variant (also known as c.2122C>T), located in coding exon 17 of the BAP1 gene, results from a C to T substitution at nucleotide position 2122. The arginine at codon 708 is replaced by tryptophan, an amino acid with dissimilar 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. |