Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000047926 | SCV000075939 | likely benign | Hereditary breast ovarian cancer syndrome | 2024-02-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000223325 | SCV000277041 | likely benign | Hereditary cancer-predisposing syndrome | 2019-04-15 | 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. |
| Center for Genomic Medicine, |
RCV003493428 | SCV004242852 | likely benign | not specified | 2024-02-06 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000223325 | SCV004361126 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-18 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with methionine at codon 89 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Functional studies have reported that this variant does not impact BRCA1 function in a homology-directed DNA repair and a haploid cell proliferation assay (PMID: 25823446, 30209399). This variant has been detected in a breast cancer case-control meta-analysis in 1/60466 cases and 1/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_006583). A multifactorial analysis has reported likelihood ratios for pathogenicity based on co-occurrence and family history of 1.1768 and 0.9148, respectively (PMID: 31131967). This variant has been identified in 1/31394 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Although there is a suspicion that this variant may not be associated with disease, additional clinical studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Breast Cancer Information Core |
RCV000112171 | SCV000144859 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2004-11-25 | no assertion criteria provided | clinical testing | |
| Brotman Baty Institute, |
RCV000112171 | SCV001238183 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |