Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000222016 | SCV000273294 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-18 | criteria provided, single submitter | clinical testing | The p.L701S variant (also known as c.2102T>C), located in coding exon 14 of the BRIP1 gene, results from a T to C substitution at nucleotide position 2102. The leucine at codon 701 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV000222016 | SCV000903702 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-04 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002519666 | SCV003239726 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2024-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 701 of the BRIP1 protein (p.Leu701Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with colorectal cancer (PMID: 34250417). ClinVar contains an entry for this variant (Variation ID: 229921). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt BRIP1 protein function with a positive predictive value of 95%. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003323458 | SCV004029741 | uncertain significance | not specified | 2023-07-31 | criteria provided, single submitter | clinical testing | Variant summary: BRIP1 c.2102T>C (p.Leu701Ser) results in a non-conservative amino acid change located in the ATP-dependent helicase, C-terminal (IPR006555) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250790 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2102T>C has been reported in the literature in an individual affected with colorectal cancer without strong evidence of causality (Pearlman_2021). This report does not provide unequivocal conclusions about association of the variant with Breast Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 34250417). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |