Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002242165 | SCV001517701 | uncertain significance | Mosaic variegated aneuploidy syndrome 1 | 2020-05-04 | criteria provided, single submitter | clinical testing | 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. 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"). This variant has not been reported in the literature in individuals with BUB1B-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with arginine at codon 915 of the BUB1B protein (p.Ser915Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine. |
Ambry Genetics | RCV002438749 | SCV002747535 | uncertain significance | Inborn genetic diseases | 2023-10-08 | criteria provided, single submitter | clinical testing | The p.S915R variant (also known as c.2745T>A), located in coding exon 21 of the BUB1B gene, results from a T to A substitution at nucleotide position 2745. The serine at codon 915 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
St. |
RCV002242165 | SCV004031153 | uncertain significance | Mosaic variegated aneuploidy syndrome 1 | 2023-08-30 | criteria provided, single submitter | clinical testing | The BUB1B c.2745T>A (p.Ser915Arg) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a deleterious effect on protein function, but this prediction has not been confirmed by functional studies. This variant has not been reported in individuals with mosaic variegated aneuploidy syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |