Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002241491 | SCV001407694 | uncertain significance | Mosaic variegated aneuploidy syndrome 1 | 2019-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 704 of the BUB1B protein (p.Pro704Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BUB1B-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV003339547 | SCV004058581 | uncertain significance | Inborn genetic diseases | 2023-06-26 | criteria provided, single submitter | clinical testing | The p.P704L variant (also known as c.2111C>T), located in coding exon 16 of the BUB1B gene, results from a C to T substitution at nucleotide position 2111. The proline at codon 704 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |