Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000471509 | SCV000549274 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2016-04-01 | 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. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA1-related disease. This sequence change replaces asparagine with isoleucine at codon 569 of the BRCA1 protein (p.Asn569Ile). The asparagine residue is moderately conserved and there is a large physicochemical difference between asparagine and isoleucine. |
Ambry Genetics | RCV002402272 | SCV002710483 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-28 | criteria provided, single submitter | clinical testing | The p.N569I variant (also known as c.1706A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 1706. The asparagine at codon 569 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
University of Washington Department of Laboratory Medicine, |
RCV002402272 | SCV003851100 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |