Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000165675 | SCV000216413 | benign | Hereditary cancer-predisposing syndrome | 2021-05-28 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
| Invitae | RCV001041837 | SCV001205482 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-11-19 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1807 of the BRCA1 protein (p.Ile1807Val). This variant is present in population databases (rs786202721, gnomAD 0.007%). This missense change has been observed in individual(s) with breast cancer (PMID: 31907386). ClinVar contains an entry for this variant (Variation ID: 186137). 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 with a negative predictive value of 95%. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30209399, 30257991). RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. |
| Color Diagnostics, |
RCV000165675 | SCV001352268 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-21 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 1807 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Functional studies have reported that this variant does not impact BRCA1 function in a haploid cell proliferation assay, phosphopeptide binding, localization after mitomycin C treatment and in a homology-mediated DNA repair assay (PMID: 30209399, 30257991). This variant has been reported in an individual affected with breast cancer (PMID: 35177575) and in a breast cancer case-control meta-analysis in 1/60466 cases and 0/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_001749). This variant has been identified in 1/251496 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Brotman Baty Institute, |
RCV001077384 | SCV001243304 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |