Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001216428 | SCV001388225 | likely pathogenic | Familial cancer of breast | 2019-04-22 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the BARD1 gene (p.Leu679*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 99 amino acids of the BARD1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BARD1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the BRCT domain of the BARD1 protein, which is essential for promoting chromosome stability and homology-directed DNA repair (PMID: 17848578). While functional studies have not been performed to directly test the effect of this variant on BARD1 protein function, this suggests that disruption of this region of the protein is causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Myriad Genetics, |
RCV001216428 | SCV004045321 | pathogenic | Familial cancer of breast | 2023-05-25 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |