Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000215027 | SCV000277557 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-12 | criteria provided, single submitter | clinical testing | The p.W1002C variant (also known as c.3006G>C), located in coding exon 19 of the BRIP1 gene, results from a G to C substitution at nucleotide position 3006. The tryptophan at codon 1002 is replaced by cysteine, an amino acid with highly 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 |
RCV005222839 | SCV005870095 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2024-04-24 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 1002 of the BRIP1 protein (p.Trp1002Cys). This variant is present in population databases (rs546083449, gnomAD 0.0009%). 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: 233222). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |