Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000534668 | SCV000636028 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 1777 of the BRCA1 protein (p.Thr1777Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 91648). 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. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30209399). 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. |
Sharing Clinical Reports Project |
RCV000077165 | SCV000108962 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2010-04-28 | no assertion criteria provided | clinical testing | |
Brotman Baty Institute, |
RCV000077165 | SCV001242626 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |