Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000774929 | SCV000908986 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-30 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with arginine at codon 1759 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). A functional study has reported that this variant does not impact BRCA1 function in a haploid human cell proliferation assay (PMID: 30209399). This variant has been detected in an individual affected with breast cancer (Color internal data). 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. |
| Invitae | RCV001854450 | SCV002275201 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-09-23 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30209399). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 96947). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 1759 of the BRCA1 protein (p.Lys1759Arg). |
| Ambry Genetics | RCV000774929 | SCV002645201 | likely benign | Hereditary cancer-predisposing syndrome | 2022-10-17 | 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. |
| Sharing Clinical Reports Project |
RCV000083068 | SCV000115142 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2009-02-25 | no assertion criteria provided | clinical testing | |
| Brotman Baty Institute, |
RCV000083068 | SCV001242989 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |