ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.329dup (p.Glu111fs) (rs80357604)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031101 SCV000299442 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000195362 SCV000076145 pathogenic Hereditary breast and ovarian cancer syndrome 2019-10-07 criteria provided, single submitter clinical testing This sequence change inserts 1 nucleotide in exon 6 of the BRCA1 mRNA (c.329dupA), causing a frameshift at codon 111. This creates a premature translational stop signal (p.Glu111Glyfs*3) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic. This particular change has been reported in the literature in individuals with breast and/or ovarian cancer (PMID: 20858050, 22762150, 10644434, 25452441, 15146556, 26577449). This variant is also known as 448insA in the literature. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000048132 SCV000210000 pathogenic not provided 2017-10-09 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA1 is denoted c.329dupA at the cDNA level and p.Glu111GlyfsX3 (E111GfsX3) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA1 448dupA or 448insA. The normal sequence, with the base that is duplicated in brackets, is CAAAAA[dupA]GGAA. The duplication causes a frameshift which changes a Glutamic Acid to a Glycine at codon 111, and creates a premature stop codon at position 3 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.329dupA was observed in multiple individuals with a personal and family history of breast and/or ovarian cancer (Wagner 1999, Meindl 2002, Reeves 2004, George 2016, Rummel 2017). We consider this variant to be pathogenic.
Michigan Medical Genetics Laboratories,University of Michigan RCV000031101 SCV000267681 pathogenic Breast-ovarian cancer, familial 1 2016-04-21 criteria provided, single submitter clinical testing
GeneKor MSA RCV000239071 SCV000296785 pathogenic Familial cancer of breast 2016-07-01 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031101 SCV000325604 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031101 SCV000489151 pathogenic Breast-ovarian cancer, familial 1 2016-08-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV000575183 SCV000665804 pathogenic Hereditary cancer-predisposing syndrome 2018-08-13 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000048132 SCV000887664 pathogenic not provided 2018-04-25 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031101 SCV000053697 pathogenic Breast-ovarian cancer, familial 1 2012-03-02 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031101 SCV000145076 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000195362 SCV000587047 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.