Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000566912 | SCV000661504 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-11-10 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Co-occurence with a mutation in another gene that clearly explains a proband's phenotype,In silico models in agreement (benign),Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes) |
| Invitae | RCV000636126 | SCV000757558 | uncertain significance | Familial cancer of breast; Fanconi anemia, complementation group J | 2018-12-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with arginine at codon 102 of the BRIP1 protein (p.Gln102Arg). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and arginine. 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. 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 tolerated, 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. |