Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000559459 | SCV000651887 | uncertain significance | BAP1-related tumor predisposition syndrome | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 135 of the BAP1 protein (p.Pro135Leu). This variant is present in population databases (rs374928824, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with BAP1-related cancer (PMID: 35441217). ClinVar contains an entry for this variant (Variation ID: 472700). 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. |
| Color Diagnostics, |
RCV000580648 | SCV000682624 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-14 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with leucine at codon 135 of the BAP1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 20/282880 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. |
| Ambry Genetics | RCV000580648 | SCV001183399 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-30 | criteria provided, single submitter | clinical testing | The p.P135L variant (also known as c.404C>T), located in coding exon 6 of the BAP1 gene, results from a C to T substitution at nucleotide position 404. The proline at codon 135 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV001559071 | SCV001781142 | uncertain significance | not provided | 2023-04-25 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with clear cell renal carcinoma (Yngvadottir et al., 2022); This variant is associated with the following publications: (PMID: 35441217) |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV002252167 | SCV002523020 | uncertain significance | See cases | 2022-01-24 | criteria provided, single submitter | clinical testing |