Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002363763 | SCV002625946 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-21 | criteria provided, single submitter | clinical testing | The p.F1245C variant (also known as c.3734T>G), located in coding exon 19 of the BRIP1 gene, results from a T to G substitution at nucleotide position 3734. The phenylalanine at codon 1245 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is poorly 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 |
RCV003094333 | SCV002998429 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 1245 of the BRIP1 protein (p.Phe1245Cys). 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: 1734413). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |