Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000132496 | SCV000187590 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-23 | criteria provided, single submitter | clinical testing | The p.K527N variant (also known as c.1581G>C), located in coding exon 9 of the BRCA1 gene, results from a G to C substitution at nucleotide position 1581. The lysine at codon 527 is replaced by asparagine, 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. |
| Color Diagnostics, |
RCV000132496 | SCV000911189 | likely benign | Hereditary cancer-predisposing syndrome | 2015-11-25 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001313648 | SCV001504152 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-07-06 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 527 of the BRCA1 protein (p.Lys527Asn). This variant is present in population databases (rs80357493, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 54300). 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 with a negative predictive value of 95%. 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, |
RCV000132496 | SCV003851192 | 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). |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003476946 | SCV004222570 | uncertain significance | not provided | 2023-06-07 | criteria provided, single submitter | clinical testing | In a large-scale breast cancer association study, the variant was observed in an individual with breast cancer as well as in an unaffected individual (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/BRCA1)). The frequency of this variant in the general population, 0.000008 (2/250470 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Breast Cancer Information Core |
RCV000111650 | SCV000144137 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion criteria provided | clinical testing |