ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.346del (p.Glu116fs) (rs762635795)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
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) RCV000238656 SCV000299446 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000238656 SCV000296474 likely pathogenic Breast-ovarian cancer, familial 1 2016-05-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV000561042 SCV000668435 pathogenic Hereditary cancer-predisposing syndrome 2019-11-04 criteria provided, single submitter clinical testing The c.346delG pathogenic mutation, located in coding exon 5 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 346, causing a translational frameshift with a predicted alternate stop codon (p.E116Nfs*3). <span style="font-family:arial,sans-serif; font-size:10pt">This alteration has been reported in at least two affected individuals with breast and/or ovarian cancer (Singh J et al. Breast Cancer Res. Treat., 2018 Jul;170:189-196). In addition to the clinical data presented in the literature, 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.
Counsyl RCV000238656 SCV000677845 likely pathogenic Breast-ovarian cancer, familial 1 2016-12-06 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759522 SCV000888892 likely pathogenic not provided 2018-01-28 criteria provided, single submitter clinical testing
Invitae RCV000804382 SCV000944291 pathogenic Hereditary breast and ovarian cancer syndrome 2019-04-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu116Asnfs*3) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs762635795, ExAC 0.006%). This variant has been observed in individuals affected with breast and/or ovarian cancer (PMID: 29470806). ClinVar contains an entry for this variant (Variation ID: 252400). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.

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.