ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.140G>A (p.Cys47Tyr) (rs80357150)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000775194 SCV000909420 likely pathogenic Hereditary cancer-predisposing syndrome 2018-06-12 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000258496 SCV000325064 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590698 SCV000698863 uncertain significance not provided 2016-07-08 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.140G>A (p.Cys47Tyr) variant causes a missense change in the RING domain, which authors have implicated that this variant is "likely to result in a defective protein, since this cysteine is a major constituent of the BRCA1 ring finger" (Ithier_1996), along with 4/5 in silico tools predicting a damaging outcome, although these predictions/assumptions have not been functionally assessed. The variant of interest was not observed in controls (1000 Gs, ExAC, or ESP). Multiple publications have cited the variant in affected individuals, predominantly referencing the same French patient originally reported by Ithier_1996, although Lai_2016 reports one New Zealand patient with limited information (ie, only states patient was refered for genetic testing with no additional information). Multiple publications cite the variant as "disease-causing," although with limited information, predominantly based on in silico programs. The UMD database cites the variant in 28 individuals with a classification of "Causal," with no additional information for an independent evaluation. Therefore, taking all available lines of evidence, ie, location of variant, in silico predictions, database classification, the variant of interest has been classified as a "VUS-possibly pathogenic," until additional information becomes available.

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