Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000130818 | SCV000185714 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-11-30 | criteria provided, single submitter | clinical testing | The p.K1179Q variant (also known as c.3535A>C), located in coding exon 9 of the BRCA1 gene, results from an A to C substitution at nucleotide position 3535. The lysine at codon 1179 is replaced by glutamine, 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 | RCV000196802 | SCV000254976 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-04-15 | 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: 142028). This missense change has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 25980754). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1179 of the BRCA1 protein (p.Lys1179Gln). |
| Counsyl | RCV000412247 | SCV000488143 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-02-19 | criteria provided, single submitter | clinical testing | |
| University of Washington Department of Laboratory Medicine, |
RCV000130818 | SCV003850371 | 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). |