ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3759_3760del (p.Lys1254fs) (rs80357520)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223389 SCV000277585 pathogenic Hereditary cancer-predisposing syndrome 2017-11-09 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) RCV000031125 SCV000144863 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Color RCV000223389 SCV000683132 pathogenic Hereditary cancer-predisposing syndrome 2016-10-24 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031125 SCV000325744 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) RCV000031125 SCV000300007 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 RCV000254638 SCV000209884 pathogenic not provided 2018-06-15 criteria provided, single submitter clinical testing This deletion of two nucleotides in BRCA1 is denoted c.3759_3760delTA at the cDNA level and p.Lys1254GlufsX12 (K1254EfsX12) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TGTC[delTA]AGAA. The deletion causes a frameshift, which changes a Lysine to a Glutamic Acid at codon 1254, and creates a premature stop codon at position 12 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.3759_3760delTA, also reported as 3878delTA using alternate nomenclature, has been published in association with breast and ovarian cancer in several individuals of Hispanic descent (John 2007, Villarreal-Garza 2015, Rebbeck 2016) and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000587721 SCV000699070 pathogenic Hereditary breast and ovarian cancer syndrome 2017-03-17 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3759_3760delTA (p.Lys1254Glufs) 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.3761_3762insTT, p.Lys1254fs). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 121388 control chromosomes and was reported in numerous affected individuals in the literature. This variant has been reported in many affected individuals. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000254638 SCV000296288 pathogenic not provided 2015-02-18 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031125 SCV000053724 pathogenic Breast-ovarian cancer, familial 1 2012-03-26 no assertion criteria provided clinical testing

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