Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000167239 | SCV000218076 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-30 | criteria provided, single submitter | clinical testing | The p.N961H variant (also known as c.2881A>C), located in coding exon 9 of the BRCA1 gene, results from an A to C substitution at nucleotide position 2881. The asparagine at codon 961 is replaced by histidine, an amino acid with similar properties. 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 | RCV001052361 | SCV001216570 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 961 of the BRCA1 protein (p.Asn961His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 32101877). ClinVar contains an entry for this variant (Variation ID: 187504). 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, |
RCV000167239 | SCV003849284 | 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). |
| Center for Precision Medicine, |
RCV002250582 | SCV002520881 | uncertain significance | Familial cancer of breast | no assertion criteria provided | curation |