Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001229542 | SCV001401989 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2022-08-09 | criteria provided, single submitter | clinical testing | 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 histidine 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: 956689). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 455 of the BRIP1 protein (p.Tyr455His). |
| ARUP Laboratories, |
RCV003117856 | SCV003799830 | uncertain significance | not provided | 2022-06-22 | criteria provided, single submitter | clinical testing | The BRIP1 c.1363T>C, p.Tyr455His variant (rs587780826), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The tyrosine at codon 455 is weakly and computational analyses predict that this variant is neutral (REVEL: 0.074). Due to limited information, the clinical significance of this variant is uncertain at this time. |