ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4903G>T (p.Glu1635Ter) (rs200432771)

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Total submissions: 8
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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) RCV000112420 SCV000300171 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000129569 SCV000184351 pathogenic Hereditary cancer-predisposing syndrome 2019-02-06 criteria provided, single submitter clinical testing The p.E1635* pathogenic mutation (also known as c.4903G>T), located in coding exon 14 of the BRCA1 gene, results from a G to T substitution at nucleotide position 4903. This changes the amino acid from a glutamic acid to a stop codon within coding exon 14. This mutation was previously identified in a breast and ovarian cancer family of Southern Chinese ancestry (Kwong A et al. PLoS ONE 2012; 7:e43994). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112420 SCV000326061 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000496337 SCV001582578 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu1635*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected breast and/or ovarian cancer (PMID: 22970155). ClinVar contains an entry for this variant (Variation ID: 55311). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Research and Development, ARUP Laboratories RCV001663953 SCV001877269 pathogenic Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2013-12-01 criteria provided, single submitter curation
Breast Cancer Information Core (BIC) (BRCA1) RCV000112420 SCV000145206 uncertain significance Breast-ovarian cancer, familial 1 2013-02-20 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496337 SCV000587432 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Brotman Baty Institute,University of Washington RCV000112420 SCV001243815 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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