ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2338C>G (p.Gln780Glu) (rs80356945)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165128 SCV000215838 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000199021 SCV000254960 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-01-20 criteria provided, single submitter clinical testing This sequence change replaces glutamine with glutamic acid at codon 780 of the BRCA1 protein (p.Gln780Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 91584). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on BRCA1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000657140 SCV000570895 uncertain significance not provided 2018-05-02 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.2338C>G at the cDNA level, p.Gln780Glu (Q780E) at the protein level, and results in the change of a Glutamine to a Glutamic Acid (CAG>GAG). Using alternate nomenclature, this variant would be defined as BRCA1 2457C>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Gln780Glu was not observed in large population cohorts (Lek 2016). This variant is located in DNA binding domain and a region known to interact with multiple other proteins (Narod 2004, Paul 2014). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRCA1 Gln780Glu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000481550 SCV000600282 uncertain significance not specified 2017-05-09 criteria provided, single submitter clinical testing
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000165128 SCV000803152 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-23 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769718 SCV000901138 uncertain significance Breast and/or ovarian cancer 2016-12-23 criteria provided, single submitter clinical testing
Color RCV000165128 SCV000906510 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-23 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077101 SCV000108898 uncertain significance Breast-ovarian cancer, familial 1 2011-11-22 no assertion criteria provided clinical testing

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