Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000584283 | SCV000688377 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-06 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000584283 | SCV001175845 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-30 | criteria provided, single submitter | clinical testing | The p.E761A variant (also known as c.2282A>C), located in coding exon 9 of the BRCA1 gene, results from an A to C substitution at nucleotide position 2282. The glutamic acid at codon 761 is replaced by alanine, an amino acid with 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. |
Invitae | RCV001368299 | SCV001564688 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-03-15 | 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: 54520). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 761 of the BRCA1 protein (p.Glu761Ala). |
Gene |
RCV001762162 | SCV002000180 | uncertain significance | not provided | 2020-10-21 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
University of Washington Department of Laboratory Medicine, |
RCV000584283 | SCV003847789 | 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 |
RCV000111815 | SCV000144365 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2004-11-25 | no assertion criteria provided | clinical testing | |
KCCC/NGS Laboratory, |
RCV000111815 | SCV003927168 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-05-05 | no assertion criteria provided | clinical testing | a variant of uncertain significance was detected in the BRCA1 gene (c.2282A>C).The p.Glu761Alavariant (also known as c.2282A>C), located in coding exon 10 (NM_007300.3) of the BRCA1 gene, results from an A to C substitution at nucleotide position 2282. The glutamic acid at codon 761 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is not well conserved (PhyloP=0.39) .This variant does not have a gnomAD exomes entry, but its locus is covered in gnomAD exomes. ClinVar contains an entry for this variant (Variation ID: 54520). In addition, this alteration is predicted to be tolerated by in silico analysis.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. |