Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000649778 | SCV000771611 | uncertain significance | BAP1-related tumor predisposition syndrome | 2023-06-04 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 539907). This variant has not been reported in the literature in individuals affected with BAP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 401 of the BAP1 protein (p.Tyr401Cys). |
| Gene |
RCV001756087 | SCV002005386 | uncertain significance | not provided | 2019-08-29 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002343351 | SCV002651225 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-02-21 | criteria provided, single submitter | clinical testing | The p.Y401C variant (also known as c.1202A>G), located in coding exon 12 of the BAP1 gene, results from an A to G substitution at nucleotide position 1202. The tyrosine at codon 401 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is well 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. |
| Baylor Genetics | RCV000649778 | SCV004213185 | uncertain significance | BAP1-related tumor predisposition syndrome | 2023-10-18 | criteria provided, single submitter | clinical testing |