Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000048137 | SCV000076150 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-12-17 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 1103 of the BRCA1 protein (p.Cys1103Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 54832). 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 with a negative predictive value of 95%. 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 | RCV000570505 | SCV000661064 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-19 | criteria provided, single submitter | clinical testing | The p.C1103F variant (also known as c.3308G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 3308. The cysteine at codon 1103 is replaced by phenylalanine, an amino acid with highly 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. |
| Counsyl | RCV000112055 | SCV000785856 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2017-12-27 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000758810 | SCV000887666 | uncertain significance | not provided | 2023-08-24 | criteria provided, single submitter | clinical testing | In the published literature, this variant has been reported to be located in a region of the BRCA1 gene that is tolerant to missense sequence changes (PMID: 31911673 (2020)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| University of Washington Department of Laboratory Medicine, |
RCV000570505 | SCV003847002 | 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). |
| Breast Cancer Information Core |
RCV000112055 | SCV000144708 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 1998-11-30 | no assertion criteria provided | clinical testing |