Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000165967 | SCV000216724 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-11-23 | criteria provided, single submitter | clinical testing | The c.3066delA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 3066, causing a translational frameshift with a predicted alternate stop codon (p.V1023*). This variant was reported in 1/60,466 breast cancer cases and in 0/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This alteration was also 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. |
| Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000258307 | SCV000325549 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000475578 | SCV000549355 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-12-25 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Val1023*) 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). 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: 186381). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000478424 | SCV000570224 | pathogenic | not provided | 2017-07-13 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA1 c.3066delA at the cDNA level and p.Val1023Ter (V1023X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA1 c.3185delA. The substitution creates a nonsense variant, which changes a Valine to a premature stop codon (GTG>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000478424 | SCV000600315 | pathogenic | not provided | 2017-05-24 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV000478424 | SCV003826626 | likely pathogenic | not provided | 2022-12-12 | criteria provided, single submitter | clinical testing |