Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000195543 | SCV000255164 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 945 of the BRIP1 protein (p.Glu945Gln). 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: 216795). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRIP1 protein function with a negative predictive value of 80%. 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, |
RCV000775411 | SCV000909756 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-03 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000775411 | SCV001177714 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-10 | criteria provided, single submitter | clinical testing | The p.E945Q variant (also known as c.2833G>C), located in coding exon 18 of the BRIP1 gene, results from a G to C substitution at nucleotide position 2833. The glutamic acid at codon 945 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly 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. |
Gene |
RCV001785514 | SCV002028092 | uncertain significance | not provided | 2021-11-10 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 11301010) |