Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000570309 | SCV000661599 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-05-30 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Insufficient evidence |
| Invitae | RCV000456342 | SCV000547343 | uncertain significance | Familial cancer of breast; Fanconi anemia, complementation group J | 2018-01-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 848 of the BRIP1 protein (p.Arg848Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 407850). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |