Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000690782 | SCV000818508 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 252 of the BRIP1 protein (p.Thr252Ile). 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: 570022). 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 expected to disrupt BRIP1 protein function with a positive 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 | RCV001026565 | SCV001188971 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-24 | criteria provided, single submitter | clinical testing | The p.T252I variant (also known as c.755C>T), located in coding exon 6 of the BRIP1 gene, results from a C to T substitution at nucleotide position 755. The threonine at codon 252 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Baylor Genetics | RCV003459683 | SCV004217060 | uncertain significance | Familial cancer of breast | 2023-07-12 | criteria provided, single submitter | clinical testing |