Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000566780 | SCV000665874 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-05 | criteria provided, single submitter | clinical testing | The p.E572K variant (also known as c.1714G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 1714. The glutamic acid at codon 572 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
Labcorp Genetics |
RCV001370219 | SCV001566686 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2020-10-24 | 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. This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 481462). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 572 of the BRCA1 protein (p.Glu572Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. |
University of Washington Department of Laboratory Medicine, |
RCV000566780 | SCV003851088 | 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). |