ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4113del (p.Cys1372fs) (rs80357861)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
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) RCV000112262 SCV000282323 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112262 SCV000325852 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000551100 SCV000635943 pathogenic Hereditary breast and ovarian cancer syndrome 2018-08-16 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 11 of the BRCA1 mRNA (c.4113delG), causing a frameshift at codon 1372. This creates a premature translational stop signal (p.Cys1372Valfs*21) 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 observed in several individuals affected with breast and/or ovarian cancer (PMID: 10464631, 26014432). This variant is also known as c.4232delG in the literature. ClinVar contains an entry for this variant (Variation ID: 125680). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000112262 SCV000677651 pathogenic Breast-ovarian cancer, familial 1 2016-11-28 criteria provided, single submitter clinical testing
GeneKor MSA RCV000585711 SCV000693532 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
GeneDx RCV000585711 SCV000779102 pathogenic not provided 2017-08-10 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.4113delG at the cDNA level and p.Cys1372ValfsX21 (C1372VfsX21) at the protein level. The normal sequence, with the base that is deleted in brackets, is CTGG[delG]TGTG. The deletion causes a frameshift which changes a Cysteine to a Valine at codon 1372, and creates a premature stop codon at position 21 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.4113delG, previously reported as 4232delG using alternate nomenclature, has been seen in at least one individual undergoing clinical BRCA1/2 testing due to personal and/or family history of cancer (Judkins 2005). We consider this variant to be pathogenic.
Color RCV000776209 SCV000911362 pathogenic Hereditary cancer-predisposing syndrome 2017-03-30 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112262 SCV000144984 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Division Human Genetics,Medical University Innsbruck RCV000112262 SCV000212001 pathogenic Breast-ovarian cancer, familial 1 2015-02-11 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.