Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000688568 | SCV000816186 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-06-14 | 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: 568267). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 484 of the BRCA1 protein (p.Gly484Arg). |
| Color Diagnostics, |
RCV001177424 | SCV001341644 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-13 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001177424 | SCV002698185 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-21 | criteria provided, single submitter | clinical testing | The p.G484R variant (also known as c.1450G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 1450. The glycine at codon 484 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species, and arginine is the reference amino acid in other 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, |
RCV001177424 | SCV003851291 | 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). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003317341 | SCV004021084 | uncertain significance | not specified | 2023-06-01 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.1450G>A (p.Gly484Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251280 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1450G>A in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters have submitted clinical-significance assessments for this variant to ClinVar after 2014. Three of these submitters classified the variant as a variant of uncertain significance, and one classified it as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| All of Us Research Program, |
RCV004004284 | SCV004818327 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-06-28 | criteria provided, single submitter | clinical testing |