Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000160015 | SCV000210231 | uncertain significance | not provided | 2021-02-19 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with early-onset breast cancer (Purnomosari 2007); Also known as 5674C>T; This variant is associated with the following publications: (PMID: 30209399, 17972177) |
| Ambry Genetics | RCV000509851 | SCV000607987 | likely benign | Hereditary cancer-predisposing syndrome | 2021-05-20 | 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. |
| Invitae | RCV001040100 | SCV001203656 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1852 of the BRCA1 protein (p.Thr1852Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 17972177). ClinVar contains an entry for this variant (Variation ID: 182174). 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). 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, |
RCV000509851 | SCV001346391 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-05 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with isoleucine at codon 1852 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). This variant has been reported to be functional in a haploid cell proliferation assay (PMID: 30209399). This variant has been reported in an individual affected with early onset breast cancer (PMID: 17972177). 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, |
RCV001078072 | SCV001244114 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |