Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000532230 | SCV000651842 | uncertain significance | BAP1-related tumor predisposition syndrome | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 353 of the BAP1 protein (p.Ile353Thr). This variant is present in population databases (rs754217069, gnomAD 0.003%). This missense change has been observed in individual(s) with breast cancer (PMID: 33646313). ClinVar contains an entry for this variant (Variation ID: 472657). 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, |
RCV000774740 | SCV000908687 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-02 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with threonine at codon 353 of the BAP1 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251410 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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 | RCV000774740 | SCV002712129 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-10 | criteria provided, single submitter | clinical testing | The p.I353T variant (also known as c.1058T>C), located in coding exon 11 of the BAP1 gene, results from a T to C substitution at nucleotide position 1058. The isoleucine at codon 353 is replaced by threonine, an amino acid with similar properties. This amino acid position is well 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 |
RCV003319376 | SCV004023741 | uncertain significance | not provided | 2023-02-02 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with breast cancer (George et al., 2021); This variant is associated with the following publications: (PMID: 33646313) |
| Baylor Genetics | RCV000532230 | SCV004213220 | uncertain significance | BAP1-related tumor predisposition syndrome | 2023-09-08 | criteria provided, single submitter | clinical testing |