ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3371_3372TC[2] (p.Pro1126fs) (rs80357828)

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Total submissions: 8
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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) RCV000112082 SCV000299935 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneKor MSA RCV000238746 SCV000296795 pathogenic Ovarian cancer 2016-07-01 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112082 SCV000325637 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000486419 SCV000568412 pathogenic not provided 2019-01-10 criteria provided, single submitter clinical testing This deletion of two nucleotides in BRCA1 is denoted c.3375_3376delTC at the cDNA level and p.Pro1126IlefsX6 (P1126IfsX6) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TCTC[delTC]CATA. The deletion causes a frameshift which changes a Proline to an Isoleucine at codon 1126, and creates a premature stop codon at position 6 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.3375_3376delTC, also published as 3494delTC using alternate nomenclature, has been observed in several breast and ovarian cancer families (Kashima 2000, Fostira 2012, Stavropoulou 2013, Konstantopoulou 2014). We consider this variant to be pathogenic.
Counsyl RCV000112082 SCV000677649 pathogenic Breast-ovarian cancer, familial 1 2017-04-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586754 SCV000699027 pathogenic Hereditary breast and ovarian cancer syndrome 2017-08-17 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3375_3376delTC (p.Pro1126Ilefs) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.3403C>T (p.Gln1135X), c.3481_3491delGAAGATACTAG (p.Glu1161fs), c.3485delA (p.Asp1162fs), etc.). Multiple publications have cited the variant in unrelated HBOC patients, including evidence for cosegregation with disease in a family (e.g. Kashima 2000, Ikeda 2001, Judkins 2005, Razis 2009, Fostira 2012, Stavropoulou 2013). This variant is absent in 121146 control chromosomes from ExAC. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000486419 SCV000888888 pathogenic not provided 2018-02-08 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112082 SCV000144743 pathogenic Breast-ovarian cancer, familial 1 2004-11-25 no assertion criteria provided clinical testing

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