Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001011144 | SCV001171433 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-19 | criteria provided, single submitter | clinical testing | The p.L452F variant (also known as c.1354C>T), located in coding exon 13 of the BAP1 gene, results from a C to T substitution at nucleotide position 1354. The leucine at codon 452 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration has been identified in a patient affected with pancreatic cancer with a family history of liver and breast cancers (Shindo K et al. J. Clin. Oncol., 2017 Oct;35:3382-3390). 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. |
| Labcorp Genetics |
RCV001862774 | SCV002210927 | uncertain significance | BAP1-related tumor predisposition syndrome | 2021-02-19 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with phenylalanine at codon 452 of the BAP1 protein (p.Leu452Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with pancreatic cancer (PMID: 28767289). 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: "Probably Damaging"; 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. |
| Gene |
RCV003159170 | SCV003852870 | uncertain significance | not provided | 2022-09-30 | 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 among individuals with pancreatic cancer (Shindo et al., 2017; Hu et al., 2020); This variant is associated with the following publications: (PMID: 28767289, 32659497) |
| Baylor Genetics | RCV001862774 | SCV005053294 | uncertain significance | BAP1-related tumor predisposition syndrome | 2023-12-29 | criteria provided, single submitter | clinical testing |