Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000570449 | SCV000672825 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-01-06 | criteria provided, single submitter | clinical testing | The p.G345E variant (also known as c.1034G>A), located in coding exon 11 of the BAP1 gene, results from a G to A substitution at nucleotide position 1034. The glycine at codon 345 is replaced by glutamic acid, 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. |
| Labcorp Genetics |
RCV003767219 | SCV004650065 | uncertain significance | BAP1-related tumor predisposition syndrome | 2023-09-08 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 345 of the BAP1 protein (p.Gly345Glu). This variant is present in population databases (rs756779992, gnomAD 0.0009%). 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: 485297). This variant has not been reported in the literature in individuals affected with BAP1-related conditions. |