Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164061 | SCV000214671 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-16 | criteria provided, single submitter | clinical testing | The p.E720K variant (also known as c.2158G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 2158. The glutamic acid at codon 720 is replaced by lysine, an amino acid with similar properties. In a study of whole-exome sequencing in patients with features of Cowden syndrome (CS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS) and negative PTEN testing, this alteration was identified in 0/87 patients with CS or BRRS and 1/3476 patients from The Cancer Genome Atlas (TCGA) (Yehia L et al. PLoS Genet, 2018 04;14:e1007352). 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 | RCV001318153 | SCV001508845 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 720 of the BRCA1 protein (p.Glu720Lys). This variant is present in population databases (rs80356875, gnomAD 0.002%). This missense change has been observed in individual(s) with breast cancer (PMID: 29625052). ClinVar contains an entry for this variant (Variation ID: 54479). 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. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 26689913). 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. |
| University of Washington Department of Laboratory Medicine, |
RCV000164061 | SCV003849454 | 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 |
RCV000077506 | SCV000109306 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2010-11-23 | no assertion criteria provided | clinical testing | |
| Breast Cancer Information Core |
RCV000077506 | SCV000144314 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2011-10-19 | no assertion criteria provided | clinical testing |