Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759545 | SCV000888926 | uncertain significance | not provided | 2018-07-06 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001297855 | SCV001486892 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-05-02 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1568 of the BRCA1 protein (p.Ile1568Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 55265). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. 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 | RCV002336183 | SCV002640033 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-30 | criteria provided, single submitter | clinical testing | The p.I1568V variant (also known as c.4702A>G), located in coding exon 14 of the BRCA1 gene, results from an A to G substitution at nucleotide position 4702. The isoleucine at codon 1568 is replaced by valine, an amino acid with highly similar properties. This variant had 87.24% of wildtype activity in a transcription activation assay (Woods NT et al. NPJ Genom Med, 2016 Mar;1:). 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. |
| Breast Cancer Information Core |
RCV000112387 | SCV000145163 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2004-11-25 | no assertion criteria provided | clinical testing |