Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000048864 | SCV000076877 | pathogenic | Hereditary breast ovarian cancer syndrome | 2022-12-31 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly1738 amino acid residue in BRCA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21990134). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 10811118, 11157798, 20516115). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is expected to disrupt BRCA1 function. ClinVar contains an entry for this variant (Variation ID: 55462). This missense change has been observed in individual(s) with breast cancer and ovarian cancer (PMID: 18465347, 21918854, 23113073). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1738 of the BRCA1 protein (p.Gly1738Glu). |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000077609 | SCV000326221 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Department of Medical Genetics, |
RCV000077609 | SCV000564324 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-07-01 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001190130 | SCV001357548 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-07-21 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with glutamic acid at codon 1738 of the BRCA1 protein. Computational and in silico lines of evidence consistently support a deleterious effect on the function of the gene or gene product (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Functional studies have shown that this variant protein is defective in assays for protease sensitivity, peptide binding, phospho-peptide specificity, transcriptional activation, and a haploid cell proliferation (PMID: 10811118, 11157798, 20516115, 30209399). This variant has been reported in individuals and families affected breast cancer and ovarian cancer (PMID: 11157798, 18465347, 21918854, 23113073, 30678073, 23113073). It has been shown that this variant segregates with breast cancer in two families, including one family with five breast cancer affected members across three generations (PMID: 23113073). Variant results in a different missense amino acid change in same location as a previously established pathogenic variant (p.Gly1738Arg). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000048864 | SCV001363823 | pathogenic | Hereditary breast ovarian cancer syndrome | 2019-08-23 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.5213G>A (p.Gly1738Glu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251492 control chromosomes (gnomAD). c.5213G>A has been reported in the literature in several individuals and families affected with Hereditary Breast and Ovarian Cancer (Keshavarzi_2012, Nielsen_2016). These data indicate that the variant is very likely to be associated with disease. Multiple publications reported experimental evidence evaluating an impact on protein function, and demonstrated protein folding defect, compromised phosphopeptide binding, and decreased transcriptional activity in yeast and human cells (Hayes_2000, Lee_2010). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and they classified the variant as pathogenic (2x) / likely pathogenic (1x). Based on the evidence outlined above, the variant was classified as pathogenic. |
Genome- |
RCV000077609 | SCV001745220 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2021-07-04 | criteria provided, single submitter | clinical testing | A 46-year-old female whit metastatic unilateral breast cancer (IDC). she has history of breast cancer in her second degree relatives (her paternal aunts). |
Center for Genomic Medicine, |
RCV003321494 | SCV004026750 | pathogenic | not provided | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000077609 | SCV004216999 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2022-02-02 | criteria provided, single submitter | clinical testing | |
Sharing Clinical Reports Project |
RCV000077609 | SCV000109412 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2012-08-01 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000077609 | SCV000145397 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing | |
Brotman Baty Institute, |
RCV000077609 | SCV001237929 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro | ||
BRCAlab, |
RCV000077609 | SCV002588828 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2022-08-26 | no assertion criteria provided | clinical testing |