Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000637401 | SCV000758857 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 18 of the BRCA1 protein (p.Met18Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer and/or ovarian cancer (Invitae). ClinVar contains an entry for this variant (Variation ID: 531241). 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. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 30209399). This variant disrupts the p.Met18 amino acid residue in BRCA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17924331, 21922593, 21990134, 23161852, 23867111). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Molecular Endocrinology Laboratory, |
RCV001072375 | SCV002003989 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | criteria provided, single submitter | clinical testing | ||
| Brotman Baty Institute, |
RCV001072375 | SCV001237746 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |