ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4118_4119AG[1] (p.Glu1373_Ser1374insTer) (rs80357787)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3DMed Clinical Laboratory Inc RCV000677798 SCV000803956 pathogenic Neoplasm of the breast 2017-06-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131891 SCV000186946 pathogenic Hereditary cancer-predisposing syndrome 2017-07-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Breast Cancer Information Core (BIC) (BRCA1) RCV000031151 SCV000144988 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Color RCV000131891 SCV000688467 pathogenic Hereditary cancer-predisposing syndrome 2017-07-13 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031151 SCV000325856 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000496761 SCV000591493 pathogenic Hereditary breast and ovarian cancer syndrome criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031151 SCV000300076 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 RCV000657802 SCV000779557 pathogenic not provided 2016-12-15 criteria provided, single submitter clinical testing This deletion of two nucleotides is denoted BRCA1 c.4120_4121delAG at the cDNA level and p.Ser1374Ter (S1374X) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TGAG[delAG]TGAA. The deletion creates a nonsense variant, which changes a Serine 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.4120_4121delAG, previously reported as 4239delAG, has been observed in multiple individuals with Hereditary Breast and Ovarian Cancer (Montagna 1996, Walsh 2011, Mannan 2016). Based on currently available evidence, we consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000496761 SCV000918799 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-12 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.4120_4121delAG (p.Ser1374X) 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. The variant was absent in 274930 control chromosomes (gnomAD). The variant, c.4120_4121delAG, has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer, including one family in which it segregated with disease (Sekine_2001, Montagna_1996). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496761 SCV000587376 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031151 SCV000053751 pathogenic Breast-ovarian cancer, familial 1 2009-04-30 no assertion criteria provided clinical testing

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