Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001235183 | SCV001407859 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2019-08-21 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with phenylalanine at codon 909 of the BRIP1 protein (p.Leu909Phe). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRIP1-related conditions. 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 phenylalanine 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. 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 | RCV002430006 | SCV002741555 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-25 | criteria provided, single submitter | clinical testing | The p.L909F variant (also known as c.2725C>T), located in coding exon 18 of the BRIP1 gene, results from a C to T substitution at nucleotide position 2725. The leucine at codon 909 is replaced by phenylalanine, an amino acid with highly 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. |