Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001962458 | SCV002217132 | uncertain significance | Mosaic variegated aneuploidy syndrome 1 | 2022-03-24 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with BUB1B-related conditions. This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 58 of the BUB1B protein (p.Gln58Lys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | RCV002397957 | SCV002713734 | uncertain significance | Inborn genetic diseases | 2022-06-17 | criteria provided, single submitter | clinical testing | The p.Q58K variant (also known as c.172C>A), located in coding exon 2 of the BUB1B gene, results from a C to A substitution at nucleotide position 172. The glutamine at codon 58 is replaced by lysine, 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. |
| St. |
RCV001962458 | SCV003843076 | uncertain significance | Mosaic variegated aneuploidy syndrome 1 | 2023-03-02 | criteria provided, single submitter | clinical testing | The BUB1B c.172C>A (p.Gln58Lys) missense change has a maximum subpopulation frequency of 0.00088% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with mosaic variegated aneuploidy syndrome. In summary, the evidence currently available is insufficient to determine the role of this variant in mosaic variegated aneuploidy syndrome. It has therefore been classified as of uncertain significance. |