ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1016del (p.Lys339fs) (rs80357569)

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Total submissions: 11
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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) RCV000030967 SCV000299521 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Michigan Medical Genetics Laboratories,University of Michigan RCV000030967 SCV000195887 pathogenic Breast-ovarian cancer, familial 1 2014-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000222143 SCV000278698 pathogenic Hereditary cancer-predisposing syndrome 2018-06-07 criteria provided, single submitter clinical testing 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 RCV000030967 SCV000324929 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507496 SCV000600235 pathogenic not provided 2016-11-28 criteria provided, single submitter clinical testing
GeneDx RCV000507496 SCV000778879 pathogenic not provided 2018-07-27 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.1016delA at the cDNA level and p.Lys339ArgfsX2 (K339RfsX2) at the protein level. The normal sequence, with the base that is deleted in brackets, is GAAAAAA[delA]GGTA. The deletion causes a frameshift which changes a Lysine to an Arginine at codon 339, and creates a premature stop codon at position 2 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.1016delA, previously published as 1129delA and 1135delA using alternate nomenclature, has been reported in several individuals with a personal and/or family history of breast and/or ovarian cancer (Hagervorst 1995, Polreich 2003, Kwong 2009, Fang 2014, Rebbeck 2016). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000496871 SCV001364036 pathogenic Hereditary breast and ovarian cancer syndrome 2019-11-05 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.1016delA (p.Lys339ArgfsX2) 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. The variant was absent in 251174 control chromosomes (gnomAD). c.1016delA has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (e.g. Rebbeck_2018, Laitman_2019). These data indicate that the variant is very likely to be associated with disease. Five ClinVar submitters including one expert panel (ENIGMA) (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000030967 SCV000053558 pathogenic Breast-ovarian cancer, familial 1 2009-05-12 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000030967 SCV000143983 not provided Breast-ovarian cancer, familial 1 no assertion provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496871 SCV000587093 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000030967 SCV000733663 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing

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