Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000581538 | SCV000688449 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-02 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with alanine at codon 1246 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251274 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. |
| Ambry Genetics | RCV000581538 | SCV002621201 | likely benign | Hereditary cancer-predisposing syndrome | 2019-11-12 | 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. |
| University of Washington Department of Laboratory Medicine, |
RCV000581538 | SCV003849863 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
| Invitae | RCV003529994 | SCV004248303 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-08-01 | 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 of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 156192). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is present in population databases (rs587776488, gnomAD 0.003%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1246 of the BRCA1 protein (p.Thr1246Ala). |
| Sharing Clinical Reports Project |
RCV000144209 | SCV000189282 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2011-02-15 | no assertion criteria provided | clinical testing |