Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000704503 | SCV000833454 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-08-14 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is not expected to disrupt BRCA1 function. ClinVar contains an entry for this variant (Variation ID: 580844). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 1756 of the BRCA1 protein (p.Gln1756Arg). |
| Ambry Genetics | RCV002334379 | SCV002641243 | likely benign | Hereditary cancer-predisposing syndrome | 2021-07-12 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478442 | SCV004219449 | uncertain significance | not provided | 2023-06-01 | criteria provided, single submitter | clinical testing | To the best of our knowledge, this variant has not been reported in individuals with BRCA1-related conditions in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). A functional study reported that this variant apparently retained functional activity in a large-scale study using a haploid cell line (PMID: 30209399 (2018)). However, additional studies are required to determine the global effect of this variant on BRCA1 protein function. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Brotman Baty Institute, |
RCV001077105 | SCV001242978 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |