ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5359T>A (p.Cys1787Ser)

dbSNP: rs80357065
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077619 SCV000244399 not provided Breast-ovarian cancer, familial, susceptibility to, 1 2019-03-25 reviewed by expert panel curation To our knowledge this variant has not been seen alone. Clinical evidence in Goldgar et al 2004 (PMID: 15290653) is not applicable unless this variant is observed in cis with c.5363G>A (Variation ID 55551). We recommend that if c.5359T>A is detected in an individual, presence of c.5363G>A should be assessed. Functional assay data analysis of the c.5359T>A variant suggests that it doesn't alter protein function alone, but that it does alter function when in combination with BRCA1 c.5363G>A (PMID: 30765603; 30209399). For more information see the haplotype entry BRCA1 c.[5359T>A;5363G>A] (Variant ID 624568).
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077619 SCV000326291 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV003105785 SCV003783588 uncertain significance Hereditary breast ovarian cancer syndrome 2023-08-29 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 1787 of the BRCA1 protein (p.Cys1787Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 55548). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is not expected to disrupt BRCA1 function. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 20378548, 20516115, 28781887, 30209399). This variant disrupts the p.Cys1787 amino acid residue in BRCA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30209399, 33558524; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Color Diagnostics, LLC DBA Color Health RCV003584536 SCV004360115 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-25 criteria provided, single submitter clinical testing This missense variant replaces cysteine with serine at codon 1787 of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies reported this variant as normal compared to wild-type control in transcription activation, haploid cell proliferation, protein stability and peptide binding assays (PMID: 20516115, 28781887, 30209399). This variant has been reported in cis with BRCA1 p.Gly1788Asp in several individuals and families affected with breast and/or ovarian cancer (PMID: 16030099, 18284688, 23233716, 25628955 , 26543556, 28959512). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Sharing Clinical Reports Project (SCRP) RCV000077619 SCV000109422 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2008-04-07 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077619 SCV000145480 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2004-02-20 no assertion criteria provided clinical testing
Brotman Baty Institute, University of Washington RCV000077619 SCV001238617 not provided Breast-ovarian cancer, familial, susceptibility to, 1 no assertion provided in vitro

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