Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000558507 | SCV000633687 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2022-12-26 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1231 of the BRIP1 protein (p.Ile1231Thr). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 461163). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). |
Ambry Genetics | RCV001020896 | SCV001182440 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-26 | criteria provided, single submitter | clinical testing | The p.I1231T variant (also known as c.3692T>C), located in coding exon 19 of the BRIP1 gene, results from a T to C substitution at nucleotide position 3692. The isoleucine at codon 1231 is replaced by threonine, an amino acid with similar properties. This variant was reported in 1/60,466 breast cancer cases and in 1/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). 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. |
Color Diagnostics, |
RCV001020896 | SCV001345636 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-22 | criteria provided, single submitter | clinical testing |