Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000794221 | SCV000933615 | uncertain significance | BAP1-related tumor predisposition syndrome | 2018-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with isoleucine at codon 471 of the BAP1 protein (p.Ala471Ile). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BAP1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 | RCV002388428 | SCV002699664 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-12 | criteria provided, single submitter | clinical testing | The c.1411_1412delGCinsAT variant, located in coding exon 13 of the BAP1 gene, results from an in-frame deletion of GC and insertion of AT at nucleotide positions 1411 to 1412. This results in the substitution of the alanine residue for an isoleucine residue at codon 471, an amino acid with similar properties. This amino acid position is highly conserved through mammals but not in all available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |