Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000167298 | SCV000218141 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-27 | criteria provided, single submitter | clinical testing | The p.S1292P variant (also known as c.3874T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide position 3874. The serine at codon 1292 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001221048 | SCV001393070 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-10-18 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. 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. 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 expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 187559). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1292 of the BRCA1 protein (p.Ser1292Pro). |
Sema4, |
RCV000167298 | SCV002538249 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-26 | criteria provided, single submitter | curation | |
University of Washington Department of Laboratory Medicine, |
RCV000167298 | SCV003849727 | 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). |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477639 | SCV004219380 | uncertain significance | not provided | 2022-11-04 | criteria provided, single submitter | clinical testing | The variant has not been reported in individuals with BRCA1-related conditions in the published literature. It also has not been reported in large, multi-ethnic general populations (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 damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |