ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.97G>C (p.Glu33Gln) (rs80357066)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000049208 SCV000077221 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-06 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glutamine at codon 33 of the BRCA1 protein (p.Glu33Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual in the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 55769). Experimental studies predicted a mild impact on the function of the encoded BRCA1 protein based on analysis of E3-ligase activity and BARD1 binding in vitro (PMID: 25823446). 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.
GeneDx RCV000478523 SCV000572202 uncertain significance not provided 2018-08-07 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.97G>C at the cDNA level, p.Glu33Gln (E33Q) at the protein level, and results in the change of a Glutamic Acid to a Glutamine (GAA>CAA). Using alternate nomenclature, this variant would be defined as BRCA1 216G>C. This variant has been observed in at least one individual referred for BRCA testing (Judkins 2005). BRCA1 Glu33Gln was not observed in large population cohorts (Lek 2016). This variant is located in the RING domain and a region known to interact with multiple proteins (Borg 2010, Paul 2014). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA1 Glu33Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000049208 SCV000591238 uncertain significance Hereditary breast and ovarian cancer syndrome 2014-01-16 criteria provided, single submitter clinical testing
Color RCV000775196 SCV000909422 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-20 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000111754 SCV000144281 uncertain significance Breast-ovarian cancer, familial 1 2004-11-25 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735483 SCV000863620 uncertain significance Breast and/or ovarian cancer 2014-01-22 no assertion criteria provided clinical testing

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