Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000821901 | SCV000962675 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2018-08-20 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRIP1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 26 of the BRIP1 protein (p.Leu26Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. |
Color Diagnostics, |
RCV003584766 | SCV004360311 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-06 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with proline at codon 26 of the BRIP1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRIP1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |