Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000221905 | SCV000276992 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-25 | criteria provided, single submitter | clinical testing | The p.S653L variant (also known as c.1958C>T), located in coding exon 13 of the BRIP1 gene, results from a C to T substitution at nucleotide position 1958. The serine at codon 653 is replaced by leucine, an amino acid with dissimilar 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. |
Labcorp Genetics |
RCV000798098 | SCV000937695 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2023-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 653 of the BRIP1 protein (p.Ser653Leu). This variant is present in population databases (rs756511744, gnomAD 0.003%). 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: 232772). 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. 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. |
Sema4, |
RCV000221905 | SCV002531384 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-22 | criteria provided, single submitter | curation |