Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000111508 | SCV000299502 | 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 |
RCV000111508 | SCV000326457 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000775183 | SCV000909397 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-05-10 | 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. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least three individuals affected with breast and ovarian cancer (PMID: 27616075; BIC accession number 19838; Color internal data). 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 | RCV001853032 | SCV002196110 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-04-03 | 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: 55749). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 30257646). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala302Leufs*12) 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). |
| Ambry Genetics | RCV000775183 | SCV002683566 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-06-04 | criteria provided, single submitter | clinical testing | The c.904delG pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 904, causing a translational frameshift with a predicted alternate stop codon (p.A302Lfs*12). This alteration has been identified in multiple individuals diagnosed with breast and/or ovarian cancer (Kraus C et al. Int J Cancer, 2017 Jan;140:95-102; Hoyer J et al. BMC Cancer, 2018 Sep;18:926). Additionally, this alteration was identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Breast Cancer Information Core |
RCV000111508 | SCV000143950 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2010-12-17 | no assertion criteria provided | clinical testing |