Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000706575 | SCV000835634 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2018-02-20 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with BRCA1-related disease. This sequence change replaces isoleucine with threonine at codon 518 of the BRCA1 protein (p.Ile518Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
University of Washington Department of Laboratory Medicine, |
RCV003158081 | SCV003851216 | 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). |
Ambry Genetics | RCV003158081 | SCV004004383 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-27 | criteria provided, single submitter | clinical testing | The p.I518T variant (also known as c.1553T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide position 1553. The isoleucine at codon 518 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |