ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5319dup (p.Asn1774fs) (rs80357823)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 13
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) RCV000074358 SCV000300238 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 RCV000048927 SCV000076940 pathogenic Hereditary breast and ovarian cancer syndrome 2019-09-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn1774Glnfs*56) 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 several individuals and families affected with breast and/or ovarian cancer (PMID: 7894491, 27062684, 11938448, 18779604), and reported to segregate with disease in at least one family (PMID: 7894491). It has also been reported in an individual affected with pancreatic cancer (PMID: 25940717). This variant is also known as c.5319_5320insC or c.5438insC in the literature. ClinVar contains an entry for this variant (Variation ID: 55523). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000131363 SCV000186339 pathogenic Hereditary cancer-predisposing syndrome 2018-09-27 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000478417 SCV000296278 pathogenic not provided 2016-02-03 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000074358 SCV000326261 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000478417 SCV000564751 pathogenic not provided 2014-10-15 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA1 is denoted c.5319dupC at the cDNA level and p.Asn1774GlnfsX56 (N1774QfsX56) at the protein level. The normal sequence, with the bases that are duplicated in brackets, is TCAC[C]AACA. The duplication causes a frameshift, which changes an Asparagine to a Glutamine at codon 1774, and creates a premature stop codon at position 56 of the new reading frame. This variant is predicted to cause loss of normal protein function through protein truncation. BRCA1 c.5319dupC, previously reported as 5438dupC, has been observed in association with hereditary breast and ovarian cancer (Castilla 1994). we consider this variant to be pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000048927 SCV000591611 pathogenic Hereditary breast and ovarian cancer syndrome 2014-07-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000048927 SCV001363932 pathogenic Hereditary breast and ovarian cancer syndrome 2019-05-03 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.5319dupC (p.Asn1774GlnfsX56) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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. The variant was absent in 251376 control chromosomes. c.5319dupC has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Castilla_1994, Judkins_2005, Holter_2015, Azzollini_2016, Cardoso_2018). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five submitters including an expert panel (ENIGMA) have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000074358 SCV000039538 pathogenic Breast-ovarian cancer, familial 1 1994-12-01 no assertion criteria provided literature only
Sharing Clinical Reports Project (SCRP) RCV000074358 SCV000053839 pathogenic Breast-ovarian cancer, familial 1 2012-11-28 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000074358 SCV000145451 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048927 SCV000587492 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735454 SCV000863591 pathogenic Breast and/or ovarian cancer 2009-09-04 no assertion criteria provided clinical testing

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.