ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3868A>T (p.Lys1290Ter) (rs80357254)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Breast Cancer Information Core (BIC) (BRCA1) RCV000031135 SCV000144905 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031135 SCV000325775 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031135 SCV000300033 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Integrated Genetics/Laboratory Corporation of America RCV000048361 SCV000699078 pathogenic Hereditary breast and ovarian cancer syndrome 2017-02-20 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3868A>T (p.Lys1290X) 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.3904G>T [p.Glu1302X]; c.3937C>T [p.Gln1313X]; and c.3972_3974delinsAA [p.Met1324fsX12]). One in silico tool predicts a damaging outcome for this variant. This variant is absent in ExAC (0/121398 control chromosomes), which is a large control population database. Multiple publications cite the variant in affected individuals, along with multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000048361 SCV000076374 pathogenic Hereditary breast and ovarian cancer syndrome 2017-03-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 1290 (p.Lys1290*). It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic. This particular variant has been reported in the literature in individuals affected with breast cancer (PMID: 25428789, 12491487). For these reasons, this variant has been classified as Pathogenic.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048361 SCV000587353 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031135 SCV000053734 pathogenic Breast-ovarian cancer, familial 1 2011-03-17 no assertion criteria provided clinical testing

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