Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000824174 | SCV000965060 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-03-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 1188 of the BRCA1 protein (p.Arg1188Ser). This variant is present in population databases (no rsID available, gnomAD no frequency). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 34026625). ClinVar contains an entry for this variant (Variation ID: 252874). 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. |
| Color Diagnostics, |
RCV001183808 | SCV001349639 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-15 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with serine at codon 1188 of the BRCA1 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250944 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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. |
| Ambry Genetics | RCV001183808 | SCV002616705 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-07 | criteria provided, single submitter | clinical testing | The p.R1188S variant (also known as c.3564G>C), located in coding exon 9 of the BRCA1 gene, results from a G to C substitution at nucleotide position 3564. The arginine at codon 1188 is replaced by serine, an amino acid with dissimilar properties. This alteration was detected in a cohort of 200 individuals with a personal and/or family history of breast/ovarian cancer (Doddato G et al. Front Oncol, 2021 May;11:649435). This amino acid position is well 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. |
| University of Washington Department of Laboratory Medicine, |
RCV001183808 | SCV003850126 | 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). |
| Sharing Clinical Reports Project |
RCV000239332 | SCV000297477 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2012-10-18 | no assertion criteria provided | clinical testing |