Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000111782 | SCV000299712 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-09-08 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
| Invitae | RCV002513655 | SCV003441937 | pathogenic | Hereditary breast ovarian cancer syndrome | 2022-09-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 54488). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 22010008, 27907908, 31825140). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu730*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). |
| Breast Cancer Information Core |
RCV000111782 | SCV000144324 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 1997-11-14 | no assertion criteria provided | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001354410 | SCV001549023 | pathogenic | Malignant tumor of breast | no assertion criteria provided | clinical testing | The BRCA1 p.Glu730* variant was identified in 3 of 4678 proband chromosomes (frequency: 0.0006) from individuals or families with ovarian cancer (Chao 2016, Song 2014). The variant was also identified in dbSNP (ID: rs80357058) as "With Pathogenic allele", ClinVar (classified as pathogenic by BIC and ENIGMA), and in LOVD 3.0 (1x as pathogenic). The variant was not identified in UMD-LSDB. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.2188G>T variant leads to a premature stop codon at position 730 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the BRCA1 gene are an established mechanism of disease in BRCA1 associated cancers and is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic. |