Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000198404 | SCV000254994 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1708 of the BRCA1 protein (p.Ala1708Thr). This variant is present in population databases (rs397507243, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 37639). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 30209399). 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 | RCV000223569 | SCV000275547 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-10 | criteria provided, single submitter | clinical testing | The p.A1708T variant (also known as c.5122G>A), located in coding exon 16 of the BRCA1 gene, results from a G to A substitution at nucleotide position 5122. The alanine at codon 1708 is replaced by threonine, an amino acid with 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 amino acid position is highly 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. |
| Sharing Clinical Reports Project |
RCV000031220 | SCV000053820 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2012-01-31 | no assertion criteria provided | clinical testing | |
| Brotman Baty Institute, |
RCV000031220 | SCV001237648 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |