ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1016dup (p.Val340fs) (rs80357569)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 18
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) RCV000074359 SCV000299522 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 RCV000190459 SCV000075323 pathogenic Hereditary breast and ovarian cancer syndrome 2019-12-23 criteria provided, single submitter clinical testing This sequence change inserts 1 nucleotide in exon 10 of the BRCA1 mRNA (c.1016dupA), causing a frameshift at codon 340. This creates a premature translational stop signal (p.Val340Glyfs*6) 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 individuals with breast and/or ovarian cancer (PMID: 10441573, 15024741, 18489799, 23289006, 23199084). This variant is also known as 1135insA in the literature. ClinVar contains an entry for this variant (Variation ID: 54102). 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 RCV000129421 SCV000184191 pathogenic Hereditary cancer-predisposing syndrome 2018-05-17 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000047310 SCV000210007 pathogenic not provided 2018-07-31 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA1 is denoted c.1016dupA at the cDNA level and p.Val340GlyfsX6 (V340GfsX6) at the protein level. The normal sequence, with the base that is duplicated in brackets, is GAAAAAA[dupA]GGTA. The duplication causes a frameshift, which changes a Valine to a Glycine at codon 340, and creates a premature stop codon at position 6 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.1016dupA, previously reported as 1135insA using alternate nomenclature, has been reported in association with breast and ovarian cancer (Borg 1999, Foretova 2004, Laraqui 2013, Yablonski-Peretz 2016). BRCA1 c.1016dupA is a founder pathogenic variant in the Norwegian population; however, it is also observed in other populations (Dorum 1999, Rudkin 2006, Torres-Mejia 2014). We consider this variant to be pathogenic.
University of Washington Department of Laboratory Medicine, University of Washington RCV000074359 SCV000266026 pathogenic Breast-ovarian cancer, familial 1 2015-11-20 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000074359 SCV000296281 pathogenic Breast-ovarian cancer, familial 1 2016-02-20 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000074359 SCV000324930 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics, Oslo University Hospital RCV000074359 SCV000564329 pathogenic Breast-ovarian cancer, familial 1 2015-07-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000190459 SCV000591313 pathogenic Hereditary breast and ovarian cancer syndrome criteria provided, single submitter clinical testing
Color RCV000129421 SCV000682931 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000190459 SCV001426923 pathogenic Hereditary breast and ovarian cancer syndrome 2020-07-17 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.1016dupA (p.Val340GlyfsX6) 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 251174 control chromosomes (gnomAD). c.1016dupA has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (e.g. Simard_1994, Ramus_2007, Palma_2008, Spearman_2008, Laraqui_2013). These data indicate that the variant is very likely to be associated with disease. Ten ClinVar submitters including an expert panel (ENIGMA) (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000074359 SCV000039521 pathogenic Breast-ovarian cancer, familial 1 1994-12-01 no assertion criteria provided literature only
Sharing Clinical Reports Project (SCRP) RCV000074359 SCV000053557 pathogenic Breast-ovarian cancer, familial 1 2012-06-25 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000074359 SCV000143982 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Curoverse RCV000190459 SCV000245337 pathogenic Hereditary breast and ovarian cancer syndrome 2015-08-01 no assertion criteria provided research Frameshifts in BRCA1 are considered pathogenic, and this is a BRCA1 Val340Gly frameshift variant in exon 10
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000190459 SCV000587094 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 RCV000735524 SCV000863662 pathogenic Breast and/or ovarian cancer 2010-04-14 no assertion criteria provided clinical testing
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785394 SCV000923965 pathogenic Ovarian Neoplasms 2018-12-01 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.