Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000637365 | SCV000758821 | pathogenic | Hereditary breast ovarian cancer syndrome | 2018-04-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp353*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related disease. Two different variants (c.1058G>A and c.1059G>A) giving rise to the same protein effect observed here (p.Trp353*) have been reported in individuals affected with hereditary breast and ovarian cancer (PMID: 9150154, 25452441). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV002477403 | SCV002774308 | pathogenic | not provided | 2018-10-04 | criteria provided, single submitter | clinical testing | This frameshift variant causes the premature termination of BRCA1 protein synthesis. To the best of our knowledge, the variant has not been reported in the published literature; however, related truncating mutations at this codon have also been described as being pathogenic in families affected with breast and/or ovarian cancer in the published literature (PMIDs: 9150154 (1997), 25452441 (2015), 29310832 (2018), and 29339979 (2018)). Based on the available information, this variant is classified as pathogenic. |