Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000167923 | SCV000218571 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-04-03 | 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. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30209399). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is not expected to disrupt BRCA1 function. ClinVar contains an entry for this variant (Variation ID: 91654). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1825 of the BRCA1 protein (p.Gly1825Arg). |
| Ambry Genetics | RCV001024156 | SCV001186125 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-09-28 | criteria provided, single submitter | clinical testing | The p.G1825R variant (also known as c.5473G>A), located in coding exon 22 of the BRCA1 gene, results from a G to A substitution at nucleotide position 5473. The glycine at codon 1825 is replaced by arginine, an amino acid with dissimilar properties. One functional study found that this nucleotide substitution is functional in a high throughput genome editing haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). 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. |
| Gene |
RCV001570599 | SCV001794921 | uncertain significance | not provided | 2022-11-09 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Published functional studies demonstrate no damaging effect: variant classified as functional based on a saturation genome editing (SGE) assay measuring cell survival (Findlay et al., 2018); Also known as 5592G>A; This variant is associated with the following publications: (PMID: 30209399, 25348405) |
| Sharing Clinical Reports Project |
RCV000077171 | SCV000108968 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2011-10-04 | no assertion criteria provided | clinical testing | |
| Brotman Baty Institute, |
RCV000077171 | SCV001243430 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |