Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000230474 | SCV000290987 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 574 of the BRIP1 protein (p.Pro574Leu). This variant is present in population databases (rs377302300, gnomAD 0.03%). 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: 241630). 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. |
| Gene |
RCV000484019 | SCV000564813 | uncertain significance | not provided | 2024-02-23 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25801821) |
| Ambry Genetics | RCV000562779 | SCV000668893 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-05 | criteria provided, single submitter | clinical testing | The p.P574L variant (also known as c.1721C>T), located in coding exon 11 of the BRIP1 gene, results from a C to T substitution at nucleotide position 1721. The proline at codon 574 is replaced by leucine, an amino acid with similar properties. This variant has been reported in 1/1120 pediatric cancer patients who underwent whole genome sequencing and/or whole exome sequencing; this patient was diagnosed with adrenocortical carcinoma (Zhang J et al. N Engl J Med, 2015 Dec;373:2336-2346). 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. |
| Color Diagnostics, |
RCV000562779 | SCV000684154 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-01 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with leucine at codon 574 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 been reported in an individual affected with pediatric adrenocortical carcinoma who has TP53 p.Arg337His covariant is considered disease-causing in ClinVar (PMID: 26580448 and variation ID: 12379). This variant has been identified in 6/251410 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 | RCV003463684 | SCV004214654 | uncertain significance | Familial cancer of breast | 2024-02-26 | criteria provided, single submitter | clinical testing |