ClinVar Miner

Submissions for variant NM_007294.4(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
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.
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.
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
Integrated Genetics/Laboratory Corporation of America RCV000048361 SCV000699078 pathogenic Hereditary breast and ovarian cancer syndrome 2019-08-01 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3868A>T (p.Lys1290X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (c.3893C>A, p.Ser1298X; c.3937C>T, p.Gln1313X; c.4015G>T, p.Glu1339X). The variant was absent in 251164 control chromosomes (gnomAD). The variant, c.3868A>T, has been reported in the literature in individuals affected with breast cancer and/or ovarian cancer (Judkins_2005, Olopade_2003, Churpek_2015, Mgbemena_2017, Rebbeck_2018). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submissions including one expert panel (ENIGMA) (evaluation after 2014) classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000031135 SCV000053734 pathogenic Breast-ovarian cancer, familial 1 2011-03-17 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031135 SCV000144905 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
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

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