Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000131990 | SCV000187048 | likely benign | Hereditary cancer-predisposing syndrome | 2021-10-11 | 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 | RCV000168342 | SCV000219031 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 583 of the BRCA1 protein (p.Lys583Glu). This variant is present in population databases (rs80356928, gnomAD 0.03%). This missense change has been observed in individual(s) with breast cancer (PMID: 8531968, 34326862). This variant is also known as 1606A>G (K536E). ClinVar contains an entry for this variant (Variation ID: 91562). 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 with a negative predictive value of 95%. 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. |
Gene |
RCV000485566 | SCV000568918 | uncertain significance | not provided | 2023-06-05 | criteria provided, single submitter | clinical testing | Reported in an individual with a family history of breast and/or ovarian cancer undergoing BRCA1/2 testing (Tepebasi et al., 2021); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as 1866A>G; This variant is associated with the following publications: (PMID: 32377563, 8531968, 29884841, 31911673, Tepebasi2021[Article], 15343273) |
Color Diagnostics, |
RCV000131990 | SCV000906664 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-08 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with glutamic acid at codon 583 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a suspected hereditary breast and ovarian cancer family (DOI: 10.29058/mjwbs.798994). This variant has been identified in 7/282226 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000485566 | SCV001133497 | uncertain significance | not provided | 2019-03-05 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001192554 | SCV001360776 | uncertain significance | not specified | 2019-10-22 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.1747A>G (p.Lys583Glu) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 250824 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1747A>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters (evaluation after 2014) cite the variant, three as uncertain significance and once as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |
University of Washington Department of Laboratory Medicine, |
RCV000131990 | SCV003851066 | 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). |
CHEO Genetics Diagnostic Laboratory, |
RCV003492430 | SCV004240249 | uncertain significance | Breast and/or ovarian cancer | 2023-06-29 | criteria provided, single submitter | clinical testing | |
Sharing Clinical Reports Project |
RCV000077079 | SCV000108876 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2007-05-31 | no assertion criteria provided | clinical testing |