ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4574_4575del (p.Gln1525fs) (rs80357813)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216673 SCV000274048 pathogenic Hereditary cancer-predisposing syndrome 2017-04-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Breast Cancer Information Core (BIC) (BRCA1) RCV000077576 SCV000145120 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077576 SCV000326001 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077576 SCV000282330 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Integrated Genetics/Laboratory Corporation of America RCV000048595 SCV000918706 pathogenic Hereditary breast and ovarian cancer syndrome 2017-09-05 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.4574_4575delAA (p.Gln1525ArgfsX5) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.4603G>T, p.Glu1535X; c.4655_4658delACTT, p.Tyr1552fsX6; c.4689C>G, p.Tyr1563X). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 124462 control chromosomes from ExAC and literature. The variant was reported in the literature in individuals affected by breast or ovarian cancer (Robertson 2012, Song 2014, Greenman 1998, Fong 2009, Morgan 2010). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000048595 SCV000076608 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-12 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides from exon 14 of the BRCA1 mRNA (c.4574_4575delAA), causing a frameshift at codon 1525. This creates a premature translational stop signal (p.Gln1525Argfs*5) and 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 reported in the literature in individuals affected with breast and ovarian cancer (PMID: 9523200, 22333603, 24728189). This variant is also known as 4693delAA in the literature. ClinVar contains an entry for this variant (Variation ID: 55229). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Michigan Medical Genetics Laboratories,University of Michigan RCV000077576 SCV000267712 pathogenic Breast-ovarian cancer, familial 1 2016-04-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508650 SCV000605884 pathogenic not provided 2017-05-24 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048595 SCV000587408 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077576 SCV000109379 pathogenic Breast-ovarian cancer, familial 1 2007-05-17 no assertion criteria provided clinical testing

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