ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2214del (p.Val740fs) (rs80357574)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
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) RCV000111794 SCV000299722 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000657403 SCV000779137 pathogenic not provided 2018-09-26 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.2214delT at the cDNA level and p.Val740CysfsX13 (V740CfsX13) at the protein level. The normal sequence, with the base that is deleted in brackets, is CAGT[delT]AAAG. The deletion causes a frameshift which changes a Valine to a Cysteine at codon 740, and creates a premature stop codon at position 13 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.2214delT, previously published as BRCA1 2333delT, has been observed in a cohort of individuals that underwent BRCA1/2 testing for a personal/family history suggestive of Hereditary Breast and Ovarian Cancer (Judkins 2005). We consider this variant to be pathogenic.
Invitae RCV000810489 SCV000950692 pathogenic Hereditary breast and ovarian cancer syndrome 2019-06-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val740Cysfs*13) 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 reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333) and Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 125546). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111794 SCV000144339 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000111794 SCV000297589 pathogenic Breast-ovarian cancer, familial 1 2010-12-21 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.