Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000574108 | SCV000668961 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-27 | criteria provided, single submitter | clinical testing | The p.S1117L variant (also known as c.3350C>T), located in coding exon 19 of the BRIP1 gene, results from a C to T substitution at nucleotide position 3350. The serine at codon 1117 is replaced by leucine, an amino acid with dissimilar 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 |
RCV000702483 | SCV000831339 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2018-04-11 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with leucine at codon 1117 of the BRIP1 protein (p.Ser1117Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine. 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 disease. ClinVar contains an entry for this variant (Variation ID: 483198). 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 leucine 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478252 | SCV004220721 | uncertain significance | not provided | 2022-10-18 | criteria provided, single submitter | clinical testing | The variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003994022 | SCV004813288 | uncertain significance | not specified | 2024-02-29 | criteria provided, single submitter | clinical testing |