Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000111490 | SCV000299496 | 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. |
| Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000111490 | SCV000326453 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000772127 | SCV000905207 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-11-01 | criteria provided, single submitter | clinical testing | This variant deletes 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with high-risk breast cancer (PMID: 32380732). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Invitae | RCV001212302 | SCV001383882 | pathogenic | Hereditary breast ovarian cancer syndrome | 2022-07-31 | 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: 125465). This premature translational stop signal has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 10923033, 21520333). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp295Thrfs*3) 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). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001212302 | SCV002600414 | pathogenic | Hereditary breast ovarian cancer syndrome | 2022-10-10 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.882delA (p.Asp295ThrfsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251246 control chromosomes (gnomAD). c.882delA has been reported in the literature in at least one individual affected with breast and/or ovarian cancer (e.g. Rebbeck_2018, Incorvaia_2020). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four submitters, including an expert panel (ENIGMA), have provided assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Breast Cancer Information Core |
RCV000111490 | SCV000143932 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-06-20 | no assertion criteria provided | clinical testing |