ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1397G>A (p.Arg466Gln) (rs199540030)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132262 SCV000187345 likely benign Hereditary cancer-predisposing syndrome 2016-11-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Does not segregate with disease in family study (genes with incomplete penetrance)
GeneDx RCV000159868 SCV000209923 likely benign not specified 2015-09-24 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.
Counsyl RCV000077069 SCV000487783 uncertain significance Breast-ovarian cancer, familial 1 2015-11-17 criteria provided, single submitter clinical testing
Invitae RCV000469966 SCV000549294 likely benign not provided 2019-01-29 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000159868 SCV000588033 uncertain significance not specified 2017-04-20 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000159868 SCV000591328 uncertain significance not specified 2015-05-27 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000159868 SCV000698859 uncertain significance not specified 2019-08-27 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.1397G>A (p.Arg466Gln) results in a conservative amino acid change located in the BRCA1, serine-rich domain (IPR025994) 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 2.4e-05 in 251102 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1397G>A has been reported in the literature in a family affected with Hereditary Breast and Ovarian Cancer, but without strong evidence for causality (Zuntini_2018). This report does 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. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar (evaluation after 2014): Multiple laboratories reported the variant with conflicting assessments (3X uncertain significance, 4X benign/likely benign). Based on the evidence outlined above, the variant was classified as uncertain significance.
Color RCV000132262 SCV000911275 benign Hereditary cancer-predisposing syndrome 2016-11-14 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077069 SCV000108866 benign Breast-ovarian cancer, familial 1 2012-03-16 no assertion criteria provided clinical testing

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