Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001923450 | SCV002188070 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2021-09-18 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 1193 of the BRIP1 protein (p.Thr1193Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. 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 isoleucine 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 | RCV002458800 | SCV002613282 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-25 | criteria provided, single submitter | clinical testing | The p.T1193I variant (also known as c.3578C>T), located in coding exon 19 of the BRIP1 gene, results from a C to T substitution at nucleotide position 3578. The threonine at codon 1193 is replaced by isoleucine, 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. |