Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000509630 | SCV000607903 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-05 | criteria provided, single submitter | clinical testing | The p.F43S variant (also known as c.128T>C), located in coding exon 2 of the BRCA1 gene, results from a T to C substitution at nucleotide position 128. The phenylalanine at codon 43 is replaced by serine, an amino acid with highly dissimilar properties. A BRCA1/BARD1 interaction assay showed that p.F43S performed similar to wild-type (Starita LM et al. Genetics, 2015 Jun;200:413-22). Another functional study found this nucleotide substitution to have intermediate function 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 highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000796172 | SCV000935671 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-04-12 | 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 performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is expected to disrupt BRCA1 function. ClinVar contains an entry for this variant (Variation ID: 441341). 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 0.007%). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 43 of the BRCA1 protein (p.Phe43Ser). |
| Gene |
RCV001770388 | SCV001993140 | uncertain significance | not provided | 2020-10-16 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (Lek 2016); Published functional studies are inconclusive:intermediate effect on survival in a haploid cell line (Findlay 2018); Also known as 247T>C; This variant is associated with the following publications: (PMID: 30209399) |
| Brotman Baty Institute, |
RCV001076605 | SCV001242387 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |