ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.192T>G (p.Cys64Trp)

dbSNP: rs587781632
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University RCV000240686 SCV000265872 likely pathogenic Breast neoplasm 2015-11-01 criteria provided, single submitter research
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000258255 SCV000325185 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000687511 SCV000815083 pathogenic Hereditary breast ovarian cancer syndrome 2021-04-18 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tryptophan at codon 64 of the BRCA1 protein (p.Cys64Trp). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with breast cancer (PMID: 27257965), and in a family with breast cancer (PMID: 29446198). ClinVar contains an entry for this variant (Variation ID: 224427). This variant affects the highly conserved Cys64 residue within the N-terminal RING domain of the BRCA1 protein (PMID: 22843421). This variant has been reported to affect BRCA1 protein function (PMID: 30209399). This variant disrupts the p.Cys64 amino acid residue in BRCA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15131401, 22034289, 23397983, 18489799, 19949876, 25085752, 19287957, 24516540, 23867111, 23161852, 12915465, 23161852, 23867111, 7894491, 21042765). This suggests that this residue is clinically-significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000258255 SCV001140642 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2019-05-28 criteria provided, single submitter clinical testing
Brotman Baty Institute, University of Washington RCV000258255 SCV001242533 not provided Breast-ovarian cancer, familial, susceptibility to, 1 no assertion provided in vitro

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