ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3193dup (p.Asp1065fs) (rs80357511)

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Total submissions: 10
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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) RCV000031095 SCV000299894 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 RCV000048099 SCV000076112 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-30 criteria provided, single submitter clinical testing This sequence change inserts 1 nucleotide in exon 10 of the BRCA1 mRNA (c.3193dupG), causing a frameshift at codon 1065. This creates a premature translational stop signal (p.Asp1065Glyfs*2) and 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 to segregate with breast, ovarian, and skin cancer in a single family (PMID: 11109172). This variant is also known as c.3312insG in the literature. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000216425 SCV000273590 pathogenic Hereditary cancer-predisposing syndrome 2016-04-14 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)
GeneDx RCV000235794 SCV000293468 pathogenic not provided 2017-08-16 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA1 is denoted c.3193dupG at the cDNA level and p.Asp1065GlyfsX2 (D1065GfsX2) at the protein level. Using alternate nomenclature, this variant has been defined as BRCA1 3312insG. The normal sequence, with the base that is duplicated in brackets, is CAGT[dupG]ATGA. The duplication causes a frameshift which changes an Aspartic Acid to a Glycine at codon 1065, 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.3193dupG has been reported in association with hereditary breast and ovarian cancer (Werness 2000, Plaskocinska 2016). We consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031095 SCV000325572 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000235794 SCV000600320 pathogenic not provided 2017-03-04 criteria provided, single submitter clinical testing
Color RCV000216425 SCV000683091 pathogenic Hereditary cancer-predisposing syndrome 2016-11-17 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031095 SCV000053691 pathogenic Breast-ovarian cancer, familial 1 2009-08-08 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031095 SCV000144667 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048099 SCV000587284 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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