Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000545615 | SCV000633543 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2024-07-23 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 413 of the BRIP1 protein (p.Val413Ala). This variant is present in population databases (rs45576134, gnomAD 0.007%). 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: 461066). 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. |
Ambry Genetics | RCV001010495 | SCV001170702 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-25 | criteria provided, single submitter | clinical testing | The p.V413A variant (also known as c.1238T>C), located in coding exon 8 of the BRIP1 gene, results from a T to C substitution at nucleotide position 1238. The valine at codon 413 is replaced by alanine, an amino acid with similar 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800747 | SCV002046223 | uncertain significance | not provided | 2020-09-14 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003459209 | SCV004217127 | uncertain significance | Familial cancer of breast | 2023-05-08 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001800747 | SCV005333130 | uncertain significance | not provided | 2023-04-18 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29338072) |