Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000204481 | SCV000259343 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-08-29 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1742 of the BRCA1 protein (p.Asn1742Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 29021639). ClinVar contains an entry for this variant (Variation ID: 219464). 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BRCA1 function (PMID: 30209399, 32546644). 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. |
| Ambry Genetics | RCV000222081 | SCV000273792 | likely benign | Hereditary cancer-predisposing syndrome | 2021-03-18 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |
| Fulgent Genetics, |
RCV000487539 | SCV000575702 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-08-07 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV000487539 | SCV004837674 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-11-02 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 1742 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 conflicting impacts for this variant. This variant is reported to have no impact on BRCA1 function in a human haploid cell proliferation assay and in a mouse embryonic stem (ES) cell model in cisplatin and olaparib sensitivity assays (PMID: 30209399, 32546644) and also deleterious impact in a homology-directed DNA repair assay in the mouse ES-cell model (PMID: 32546644). This variant has been reported in an individual affected with breast cancer (PMID: 29021639) and in a breast cancer case-control meta-analysis in 0/60466 cases and 1/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_001145). This variant has not been identified 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, |
RCV000487539 | SCV001237942 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |