ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4132G>A (p.Val1378Ile) (rs28897690)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000195345 SCV000076469 benign Hereditary breast and ovarian cancer syndrome 2017-12-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130952 SCV000185866 likely benign Hereditary cancer-predisposing syndrome 2018-01-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Intact protein function observed in appropriate functional assay(s)
GeneDx RCV000048456 SCV000210168 likely benign not specified 2017-12-07 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 RCV000112269 SCV000488205 uncertain significance Breast-ovarian cancer, familial 1 2016-01-22 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000048456 SCV000591495 likely benign not specified 2016-02-10 criteria provided, single submitter clinical testing
Color RCV000130952 SCV000683154 likely benign Hereditary cancer-predisposing syndrome 2015-06-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588834 SCV000699111 likely benign not provided 2016-03-18 criteria provided, single submitter clinical testing Variant summary: The c.4132G>A variant in BRCA1 gene is a missense change that alters a non-conserved nucleotide and 5/5 in silico tools predict benign outcome. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.009% (9/102170 chromosomes). This frequency does not exceed the maximal expected allele frequency for a pathogenic variant in BRCA1 gene (0.1%); however, the frequency data may still suggests that this variant is a rare polymorphism. The variant of interest was identified in several sporadic breast cancer cases but it did not segregate with the disease in a large HBOC family (Santos, 2014). In addition, the variant was found to co-occur with a known pathogenic mutation, BRCA2 c.5213_5216delCTTA. In vitro studies showed no significant difference as compared to wild type in a functional complementation and a cisplatin growth assays (Bouwman_2013). Lastly, multiple reputable databases/diagnostic centers have classified the variant as Likely Benign. Taking together, the variant has currently been classified as Likely Benign (or Probable Normal Variant).
PreventionGenetics,PreventionGenetics RCV000588834 SCV000806945 likely benign not provided 2017-03-27 criteria provided, single submitter clinical testing
Mendelics RCV000195345 SCV000839241 likely benign Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112269 SCV000144995 uncertain significance Breast-ovarian cancer, familial 1 1999-03-24 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735522 SCV000863660 uncertain significance Breast and/or ovarian cancer 2014-06-25 no assertion criteria provided clinical testing

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