Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000538284 | SCV000651877 | uncertain significance | BAP1-related tumor predisposition syndrome | 2023-12-31 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 69 of the BAP1 protein (p.Thr69Met). This variant is present in population databases (rs572063023, gnomAD 0.009%). 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: 472690). 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 | RCV000570758 | SCV000672739 | likely benign | Hereditary cancer-predisposing syndrome | 2021-09-28 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Color Diagnostics, |
RCV000570758 | SCV000687995 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-23 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with methionine at codon 69 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 BAP1-related disorders in the literature. This variant has been identified in 11/277704 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. |
| Mendelics | RCV000538284 | SCV000838044 | uncertain significance | BAP1-related tumor predisposition syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| MGZ Medical Genetics Center | RCV000538284 | SCV002580463 | uncertain significance | BAP1-related tumor predisposition syndrome | 2021-09-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003222033 | SCV003918757 | uncertain significance | not provided | 2023-04-12 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32181510) |
| Baylor Genetics | RCV000538284 | SCV004213223 | uncertain significance | BAP1-related tumor predisposition syndrome | 2023-08-25 | criteria provided, single submitter | clinical testing |