Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003529784 | SCV004316289 | uncertain significance | BAP1-related tumor predisposition syndrome | 2023-08-11 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 184 of the BAP1 protein (p.Asp184His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BAP1-related conditions. 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 | RCV004369398 | SCV005023352 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-07 | criteria provided, single submitter | clinical testing | The p.D184H variant (also known as c.550G>C), located in coding exon 7 of the BAP1 gene, results from a G to C substitution at nucleotide position 550. The aspartic acid at codon 184 is replaced by histidine, an amino acid with similar properties. This variant has been observed in at least one individual with a personal and/or family history that is consistent with BAP1-related tumor predisposition syndrome (Ambry internal data).This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |