Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000160339 | SCV000210842 | uncertain significance | not provided | 2024-11-12 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV000222664 | SCV000275567 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-17 | criteria provided, single submitter | clinical testing | The p.P111Q variant (also known as c.332C>A), located in coding exon 3 of the BRIP1 gene, results from a C to A substitution at nucleotide position 332. The proline at codon 111 is replaced by glutamine, an amino acid with similar properties. This amino acid position is 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 |
RCV000226236 | SCV000291040 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2025-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 111 of the BRIP1 protein (p.Pro111Gln). This variant is not present in population databases (gnomAD 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: 182349). 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 not expected to disrupt BRIP1 protein function with a negative 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. |
| Color Diagnostics, |
RCV000222664 | SCV000684256 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-22 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with glutamine at codon 111 of the BRIP1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/31392 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Baylor Genetics | RCV003462084 | SCV004214674 | uncertain significance | Familial cancer of breast | 2023-10-16 | criteria provided, single submitter | clinical testing |