Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000563778 | SCV000665052 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-24 | criteria provided, single submitter | clinical testing | The p.K309E variant (also known as c.925A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 925. The lysine at codon 309 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is well 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. |
University of Washington Department of Laboratory Medicine, |
RCV000563778 | SCV003846287 | 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). |
Invitae | RCV003644951 | SCV004516100 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-01-25 | 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: 252893). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 309 of the BRCA1 protein (p.Lys309Glu). |
Sharing Clinical Reports Project |
RCV000239043 | SCV000297496 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2010-10-06 | no assertion criteria provided | clinical testing |