Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000637540 | SCV000759004 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-11-15 | 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: 531310). 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 aspartic acid, which is acidic and polar, at codon 540 of the BRCA1 protein (p.Glu540Asp). |
University of Washington Department of Laboratory Medicine, |
RCV003157766 | SCV003851167 | 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). |
Ambry Genetics | RCV003157766 | SCV003856646 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-07 | criteria provided, single submitter | clinical testing | The p.E540D variant (also known as c.1620G>C), located in coding exon 9 of the BRCA1 gene, results from a G to C substitution at nucleotide position 1620. The glutamic acid at codon 540 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, 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. |