Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000473880 | SCV000549343 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-10-04 | criteria provided, single submitter | clinical testing | Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 409332). 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 valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 83 of the BRCA1 protein (p.Val83Phe). 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. |
| Ambry Genetics | RCV002451111 | SCV002738336 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2021-11-24 | criteria provided, single submitter | clinical testing | The p.V83F variant (also known as c.247G>T), located in coding exon 4 of the BRCA1 gene, results from a G to T substitution at nucleotide position 247. The valine at codon 83 is replaced by phenylalanine, an amino acid with highly similar properties. One functional study found that this nucleotide substitution is non-functional in a high-throughput, genome editing, haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Brotman Baty Institute, |
RCV001072718 | SCV001238150 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |