Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001224243 | SCV001396430 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with valine at codon 15 of the BRCA1 protein (p.Ile15Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 12815604, 30702160). This variant is also known as c.162A>G. 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 are conflicting or provide insufficient evidence to determine the effect of this variant on BRCA1 function (PMID: 25823446, 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. |
Ambry Genetics | RCV002327373 | SCV002629099 | likely benign | Hereditary cancer-predisposing syndrome | 2021-03-11 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Brotman Baty Institute, |
RCV001072363 | SCV001237731 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |