ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.140G>T (p.Cys47Phe) (rs80357150)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Breast Cancer Information Core (BIC) (BRCA1) RCV000111876 SCV000144455 uncertain significance Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Centro de Genética y Biología Molecular,Universidad de San Martín de Porres RCV000111876 SCV000282660 likely pathogenic Breast-ovarian cancer, familial 1 2016-06-06 criteria provided, single submitter clinical testing No present in population-based study (100 controls)
Color RCV000775193 SCV000909419 likely pathogenic Hereditary cancer-predisposing syndrome 2018-09-04 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000111876 SCV000325065 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000111876 SCV000564344 likely pathogenic Breast-ovarian cancer, familial 1 2015-07-01 criteria provided, single submitter clinical testing
Department of Medical Genetics,University Hospital of North Norway RCV000111876 SCV000301425 likely pathogenic Breast-ovarian cancer, familial 1 2016-05-01 no assertion criteria provided clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781002 SCV000918747 likely pathogenic Hereditary breast and ovarian cancer syndrome 2017-12-01 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.140G>T (p.Cys47Phe) variant involves the alteration of a conserved nucleotide located in the Zinc finger, RING-type domain (InterPro). 4/5 in silico tools predict a damaging outcome for this variant. This variant is absent in 245240 control chromosomes (gnomAD and Buleje_2017). This variant has been reported in multiple affected individuals/families with HBOC (Scottish-Northern Irish Consortium_2003, Buleje_2017). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic/likely pathogenic. Functional assays provide conflicting results with some showing increased number of cells per colony (more than double) and higher cell concentration (approximately 50%) associated with this variant, while others showing results comparable to WT (Millot_2012, Houdayer_2012, and Thouvenot_2016). One study showed a predicted HDR assay (based on E3 ubiquitin ligase activity and binding to the BARD1 RING domain) of approximately 20% of WT (Starita_2015). Variant involving the same codon, such as C47G and C47Y have been reported in affected individuals and classified as likely pathogenic and VUS-possibly pathogenic by our lab, suggesting the functional importance of this codon. Taken together, this variant is currently classified as likely pathogenic until more information becomes available.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000111876 SCV000296426 pathogenic Breast-ovarian cancer, familial 1 2016-02-09 criteria provided, single submitter clinical testing

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