Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000695034 | SCV000823509 | pathogenic | Hereditary breast ovarian cancer syndrome | 2018-01-24 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant has been reported in individuals affected with breast cancer (PMID: 28724667). This sequence change creates a premature translational stop signal (p.Leu95Thrfs*23) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV002440475 | SCV002750427 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-11-12 | criteria provided, single submitter | clinical testing | The c.283_286delCTTG pathogenic mutation, located in coding exon 4 of the BRCA1 gene, results from a deletion of 4 nucleotides at nucleotide positions 283 to 286, causing a translational frameshift with a predicted alternate stop codon (p.L95Tfs*23). This alteration has been reported in multiple Chinese individuals who underwent either BRCA1/2 gene testing or multi-gene panel testing (Sun J et al. Clin Cancer Res, 2017 Oct;23:6113-6119; Shi T et al. Int J Cancer, 2017 05;140:2051-2059; Bu H et al. J Obstet Gynaecol Res, 2019 Nov;45:2267-2274; Shao D et al. Cancer Sci, 2020 Feb;111:647-657). 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. |