Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001902300 | SCV002128413 | uncertain significance | Mosaic variegated aneuploidy syndrome 1 | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1049 of the BUB1B protein (p.Phe1049Ser). This variant is present in population databases (rs751744682, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with BUB1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1363506). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV002324252 | SCV002610500 | uncertain significance | Inborn genetic diseases | 2023-11-03 | criteria provided, single submitter | clinical testing | The p.F1049S variant (also known as c.3146T>C), located in coding exon 23 of the BUB1B gene, results from a T to C substitution at nucleotide position 3146. The phenylalanine at codon 1049 is replaced by serine, an amino acid with highly dissimilar 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. |