ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.116G>T (p.Cys39Phe) (rs80357498)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000206829 SCV000259445 likely pathogenic Hereditary breast and ovarian cancer syndrome 2019-03-18 criteria provided, single submitter clinical testing This sequence change replaces cysteine with phenylalanine at codon 39 of the BRCA1 protein (p.Cys39Phe). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with increased risk of breast and/or ovarian cancer (PMID: 29446198). ClinVar contains an entry for this variant (Variation ID: 37393). This variant has been reported to affect BRCA1 protein function (PMID: 30209399). This variant disrupts the highly conserved p.Cys39 amino acid residue within the N-terminal RING domain of the BRCA1 protein (PMID: 22843421). Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9808526, 11320250, 12827452, 19543972, 21725363, 21922593, 21990134, 23161852, 24489791). This suggests that this residue is clinically-significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000030974 SCV000324975 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000509711 SCV000607989 likely pathogenic Hereditary cancer-predisposing syndrome 2019-08-16 criteria provided, single submitter clinical testing Well-characterized mutation at same position;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Sharing Clinical Reports Project (SCRP) RCV000030974 SCV000053565 pathogenic Breast-ovarian cancer, familial 1 2010-12-20 no assertion criteria provided clinical testing
Brotman Baty Institute,University of Washington RCV000030974 SCV001242368 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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