Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000563671 | SCV000673061 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-10 | criteria provided, single submitter | clinical testing | The p.K1322I variant (also known as c.3965A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 3965. The lysine at codon 1322 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000758819 | SCV000887678 | uncertain significance | not provided | 2018-01-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001321831 | SCV001512680 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 1322 of the BRCA1 protein (p.Lys1322Ile). This variant is not present in population databases (gnomAD no frequency). 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: 55060). 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, |
RCV000563671 | SCV003849388 | 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). |
| Breast Cancer Information Core |
RCV000112219 | SCV000144927 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2004-11-25 | no assertion criteria provided | clinical testing |