ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4766G>A (p.Arg1589His) (rs80357341)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000048656 SCV000076669 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-13 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1589 of the BRCA1 protein (p.Arg1589His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs80357341, ExAC 0.006%). This variant has been observed in individuals with a personal or family history of breast cancer and/or ovarian cancer (PMID: 20727672, 27886673). It is also known as 4885G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 55284). Experimental studies using transcription activation assays have shown that cells carrying this variant produce results that are similar to that of cells with wild-type BRCA1 sequence (PMID: 23613828). Another study reported that this variant produces no effect on splicing by RT-PCR analysis (PMID: 21735045). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000130538 SCV000185407 likely benign Hereditary cancer-predisposing syndrome 2017-01-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Intact protein function observed in appropriate functional assay(s),Other strong data supporting benign classification
Counsyl RCV000112396 SCV000220786 likely benign Breast-ovarian cancer, familial 1 2014-10-13 criteria provided, single submitter literature only
GeneDx RCV000442424 SCV000520101 likely benign not specified 2015-10-09 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.
Color RCV000130538 SCV000909012 likely benign Hereditary cancer-predisposing syndrome 2018-04-02 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112396 SCV000145177 uncertain significance Breast-ovarian cancer, familial 1 2007-04-10 no assertion criteria provided clinical testing

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