Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000820078 | SCV000960772 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-05-25 | criteria provided, single submitter | clinical testing | 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: 662436). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is present in population databases (rs753440254, gnomAD 0.0009%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1081 of the BRCA1 protein (p.Asn1081Ser). 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, |
RCV003158237 | SCV003849075 | 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 | RCV003158237 | SCV005100569 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-16 | criteria provided, single submitter | clinical testing | The p.N1081S variant (also known as c.3242A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 3242. The asparagine at codon 1081 is replaced by serine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |