Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002242206 | SCV001533065 | uncertain significance | Mosaic variegated aneuploidy syndrome 1 | 2020-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with alanine at codon 1026 of the BUB1B protein (p.Thr1026Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs771709698, ExAC 0.001%). 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine 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. This variant has not been reported in the literature in individuals with BUB1B-related conditions. |
Ambry Genetics | RCV002319702 | SCV002608689 | uncertain significance | Inborn genetic diseases | 2021-11-30 | criteria provided, single submitter | clinical testing | The p.T1026A variant (also known as c.3076A>G), located in coding exon 23 of the BUB1B gene, results from an A to G substitution at nucleotide position 3076. The threonine at codon 1026 is replaced by alanine, 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. |