ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3893C>A (p.Ser1298Ter) (rs80357440)

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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) RCV000077557 SCV000300037 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 RCV000212178 SCV000210161 pathogenic not provided 2014-06-04 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.3893C>A at the cDNA level and p.Ser1298Ter (S1298X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.3893C>A, previously reported as c.4012C>A using alternative nomenclature has been reported as deleterious (Judkins 2005) and observed in a German family with breast and ovarian cancer (Meindl 2002). This variant is considered pathogenic.
Ambry Genetics RCV000162869 SCV000213356 pathogenic Hereditary cancer-predisposing syndrome 2016-09-08 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)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077557 SCV000325779 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Color RCV000162869 SCV000688456 pathogenic Hereditary cancer-predisposing syndrome 2017-09-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587766 SCV000699082 pathogenic Hereditary breast and ovarian cancer syndrome 2016-12-01 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3893C>A (p.Ser1298X) 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. The variant of interest has not been observed in controls (ExAC, 1000 Gs, or ESP) and has been reported in multiple affected individuals via publications and a clinical database (BIC). In addition, multiple clinical diagnostic laboratories/databases cite the variant as "pathogenic." Therefore, the variant of interest has been classified as "Pathogenic."
Fulgent Genetics,Fulgent Genetics RCV000763002 SCV000893447 pathogenic Familial cancer of breast; Breast-ovarian cancer, familial 1; Pancreatic cancer 4; FANCONI ANEMIA, COMPLEMENTATION GROUP S 2018-10-31 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077557 SCV000109359 pathogenic Breast-ovarian cancer, familial 1 2012-06-13 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077557 SCV000144910 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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