ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3342_3345del (p.Glu1114_Glu1115insTer) (rs397509058)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077543 SCV000299927 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 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 RCV000077543 SCV000325625 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077543 SCV000488951 pathogenic Breast-ovarian cancer, familial 1 2016-08-02 criteria provided, single submitter clinical testing
GeneDx RCV000521138 SCV000617452 pathogenic not provided 2017-09-28 criteria provided, single submitter clinical testing This deletion of four nucleotides is denoted BRCA1 c.3342_3345delAGAA at the cDNA level and p.Glu1115Ter (E1115X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA1 3461_3464delAGAA. The normal sequence, with the bases that are deleted in brackets, is ATGA[delAGAA]GTAG. The deletion creates a nonsense variant, which changes a Glutamic Acid to a premature stop codon. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.3342_3345delAGAA has been observed in at least two individuals with breast and/or ovarian cancer and has been described as a recurrent variant in southern China (Kwong 2009, Kwong 2012). This variant is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000496369 SCV000699021 pathogenic Hereditary breast and ovarian cancer syndrome 2016-08-15 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3342_3345delAGAA (p.Glu1115X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. If a stable protein product is made, p.Glu1115X would lack the C-terminal BRCT domains, vital for BRCA1 function. Additionally, truncations downstream of this position have been classified as pathogenic by our laboratory (e.g.c.3748G>T/p.Glu1250X, c.3904G>T/p.Glu1302X, etc.). One in silico tool predicts a damaging outcome for this variant. This variant has been reported in at least two clinically high-risk and/or ovarian cancer patients and was absent in 121128 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Color RCV000776478 SCV000912040 pathogenic Hereditary cancer-predisposing syndrome 2017-11-26 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077543 SCV000109344 pathogenic Breast-ovarian cancer, familial 1 2012-12-17 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077543 SCV000144729 uncertain significance Breast-ovarian cancer, familial 1 2013-02-20 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496369 SCV000587303 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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