Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000164964 | SCV000215656 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-03 | criteria provided, single submitter | clinical testing | The p.K1146E variant (also known as c.3436A>G), located in coding exon 19 of the BRIP1 gene, results from an A to G substitution at nucleotide position 3436. The lysine at codon 1146 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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. |
Labcorp Genetics |
RCV000537167 | SCV000633674 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with glutamic acid at codon 1146 of the BRIP1 protein (p.Lys1146Glu). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 185524). 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 glutamic acid 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. |
Baylor Genetics | RCV003462159 | SCV004214684 | uncertain significance | Familial cancer of breast | 2023-10-10 | criteria provided, single submitter | clinical testing |