Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001385723 | SCV001585685 | pathogenic | Hereditary breast ovarian cancer syndrome | 2020-01-02 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with BRCA1-related conditions. 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 is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ala225Leufs*9) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. |
| Baylor Genetics | RCV003462918 | SCV004217020 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2021-11-27 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001355015 | SCV001549769 | pathogenic | Malignant tumor of breast | no assertion criteria provided | clinical testing | The BRCA1 p.Ala225Leufs*9 variant was not identified in the literature nor was it identified in the dbSNP, ClinVar, Gene Insight-COGR, Cosmic, LOVD 3.0, UMD-LSDB, BIC Database, ARUP Laboratories, and Zhejiang University databases. The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.672del variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 225 and leads to a premature stop codon at position 233. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the BRCA1 gene are an established mechanism of disease in breast cancer 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. |