Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000049085 | SCV000077098 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-08-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys223Argfs*11) in the BRCA1 gene. Loss-of-function variants in BRCA1 are expected to be pathogenic (PMID: 20104584). However, an in-frame BRCA1 isoform lacking exons 8 and 9 (also known as exons 9 and 10) is highly expressed in blood from unaffected individuals and in normal breast tissue; this isoform may retain protein function and could functionally rescue loss-of-function variants within exons 8-9 (PMID: 24569164). This variant is not present in population databases (gnomAD no frequency). 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: 55659). 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. |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000112758 | SCV000326374 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000112758 | SCV004216920 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2022-08-26 | criteria provided, single submitter | clinical testing | |
Breast Cancer Information Core |
RCV000112758 | SCV000145649 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 1999-04-06 | no assertion criteria provided | clinical testing |