Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000204921 | SCV000261831 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-07-06 | criteria provided, single submitter | clinical testing | 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 not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 91597). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is present in population databases (rs398122665, gnomAD 0.01%). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 902 of the BRCA1 protein (p.Glu902Asp). |
| Color Diagnostics, |
RCV000583357 | SCV000688396 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-17 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with aspartic acid at codon 902 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 36200007). This variant has been identified in 3/250872 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV000583357 | SCV001177172 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-11-10 | criteria provided, single submitter | clinical testing | The p.E902D variant (also known as c.2706A>C), located in coding exon 9 of the BRCA1 gene, results from an A to C substitution at nucleotide position 2706. The glutamic acid at codon 902 is replaced by aspartic acid, an amino acid with highly similar 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. |
| University of Washington Department of Laboratory Medicine, |
RCV000583357 | SCV003849412 | 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). |
| Sharing Clinical Reports Project |
RCV000077114 | SCV000108911 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2008-04-28 | no assertion criteria provided | clinical testing |