Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001056267 | SCV001220701 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2019-12-13 | criteria provided, single submitter | clinical testing | 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. This variant has not been reported in the literature in individuals with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with asparagine at codon 1858 of the BRCA1 protein (p.Ile1858Asn). The isoleucine residue is moderately conserved and there is a large physicochemical difference between isoleucine and asparagine. 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. |