Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000524854 | SCV000651896 | uncertain significance | BAP1-related tumor predisposition syndrome | 2024-07-19 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 196 of the BAP1 protein (p.Trp196Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 472708). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BAP1 protein function. 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 | RCV001024645 | SCV001186694 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-03-29 | criteria provided, single submitter | clinical testing | The p.W196C variant (also known as c.588G>C), located in coding exon 8 of the BAP1 gene, results from a G to C substitution at nucleotide position 588. The tryptophan at codon 196 is replaced by cysteine, an amino acid with highly dissimilar 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. |
| Center for Genomic Medicine, |
RCV004596254 | SCV005090608 | uncertain significance | not specified | 2025-03-04 | criteria provided, single submitter | clinical testing |