ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1233T>G (p.Asp411Glu) (rs80357024)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000034726 SCV000075400 likely benign not provided 2019-03-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130781 SCV000185674 likely benign Hereditary cancer-predisposing syndrome 2017-09-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: in silico models in agreement (benign),Other data supporting benign classification
GeneDx RCV000428573 SCV000517031 likely benign not specified 2017-11-21 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000034726 SCV000600244 likely benign not provided 2018-11-10 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000428573 SCV000698836 likely benign not specified 2019-03-01 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.1233T>G (p.Asp411Glu) results in a conservative amino acid change located in the serine-rich domain (IPR025994) of 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 3.4e-05 in 380942 control chromosomes (gnomAD and publication data), predominantly at a frequency of 0.00044 within the African subpopulation in the gnomAD database. Though this frequency is not higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (0.00044 vs 0.001), the variant might still represent a benign polymorphism. In addition, the variant was also reported in 1/7325 European American women (frequency: 0.00014) and 2/2559 African American women (frequency: 0.0008), who were older than age 70 years and have never had cancer (in the FLOSSIES database). c.1233T>G has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer or in individuals undergoing BRCA1/2 clinical testing without strong evidence for or against pathogenicity. These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (3 classifying it as likely benign, and 1 as a VUS). Based on the evidence outlined above, the variant was classified as likely benign.
Color RCV000130781 SCV000903235 benign Hereditary cancer-predisposing syndrome 2015-12-10 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034726 SCV000043182 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
Sharing Clinical Reports Project (SCRP) RCV000083166 SCV000115240 benign Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000083166 SCV000144035 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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