Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000566444 | SCV000661103 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-12 | criteria provided, single submitter | clinical testing | The p.F861C variant (also known as c.2582T>G), located in coding exon 9 of the BRCA1 gene, results from a T to G substitution at nucleotide position 2582. The phenylalanine at codon 861 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been classified as likely to be deleterious using a combination of a multiple sequence alignment of orthologous BRCA1 sequences (evolutionary conservation) and a measure of the chemical difference between the amino acids present at individual residues in the sequence alignment to classify missense variants (Abkevich V et al. J. Med. Genet., 2004 Jul;41:492-507). This amino acid position is highly conserved in available vertebrate species. 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. |
| University of Washington Department of Laboratory Medicine, |
RCV000566444 | SCV003847564 | 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). |
| All of Us Research Program, |
RCV000111895 | SCV004843073 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-11-30 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV005089435 | SCV005837720 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 861 of the BRCA1 protein (p.Phe861Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 16267036). ClinVar contains an entry for this variant (Variation ID: 54608). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt BRCA1 protein function with a positive predictive value of 80%. 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. |
| Breast Cancer Information Core |
RCV000111895 | SCV000144480 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2004-02-20 | no assertion criteria provided | clinical testing |