Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000129818 | SCV000184632 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-15 | criteria provided, single submitter | clinical testing | The p.P568R variant (also known as c.1703C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 1703. The proline at codon 568 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been reported in one family from a cohort of 531 individuals referred for HBOC testing based on a significant family history of breast and/or ovarian cancer (Konecny M. et al. Breast Cancer Res. Treat. 2011;126(1):119-30). In a study of 1854 high-risk breast and/or ovarian cancer families in Italy, this alteration was detected in one family (Azzollini J et al. Eur J Intern Med, 2016 Jul;32:65-71). This amino acid position is poorly 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. |
| Gene |
RCV000479365 | SCV000566924 | likely benign | not provided | 2020-09-08 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 15385441, 10923033, 27062684, 31131967, 21203900, 33087888) |
| Color Diagnostics, |
RCV000129818 | SCV000909368 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-17 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with arginine at codon 568 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in two suspected hereditary breast and ovarian cancer families (PMID: 21203900, 27062684), and a multifactorial analysis has reported likelihood ratios for pathogenicity based on tumor pathology, co-occurrence with a pathogenic variant and family history of 0.21, 1.0673 and 0.3838, respectively (PMID: 31131967). This variant has been identified in 2/250428 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Invitae | RCV001364082 | SCV001560214 | likely benign | Hereditary breast ovarian cancer syndrome | 2024-01-19 | criteria provided, single submitter | clinical testing | |
| University of Washington Department of Laboratory Medicine, |
RCV000129818 | SCV003851103 | 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 |
RCV000111667 | SCV000144160 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2004-02-20 | no assertion criteria provided | clinical testing |