ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1769_1772TTAT[1] (p.Ile591fs) (rs80359304)

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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) RCV000112966 SCV000282360 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000043880 SCV000071893 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-30 criteria provided, single submitter clinical testing This sequence change deletes 4 nucleotides from exon 10 of the BRCA2 mRNA (c.1773_1776delTTAT), causing a frameshift at codon 591. This creates a premature translational stop signal (p.Ile591Metfs*22) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic. This particular variant has been reported in the literature in individuals affected with breast cancer (PMID: 12942367, 18393245, 22923021). This varint is also known as 2001delTTAT in the literature. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000160268 SCV000210715 pathogenic not provided 2014-04-01 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.1773_1776delTTAT at the cDNA level and p.Ile591MetfsX22 (I591MfsX22) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GTTTAT[TTAT]GCTA. The deletion causes a frameshift, which changes an Isoleucine to a Methionine at codon 591, and creates a premature stop codon at position 22 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. BRCA2 c.1773_1776delTTAT, previously reported as BRCA2 2001del4 using alternate nomenclature, has been reported in association with hereditary breast and ovarian cancer (Kanaan 2003, Thirthagiri 2008, Cao 2013). We therefore consider this variant to be pathogenic.
Ambry Genetics RCV000213388 SCV000274783 pathogenic Hereditary cancer-predisposing syndrome 2018-01-04 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)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000112966 SCV000296721 pathogenic Breast-ovarian cancer, familial 2 2015-02-25 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112966 SCV000326608 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000112966 SCV000677670 pathogenic Breast-ovarian cancer, familial 2 2017-02-01 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000112966 SCV000145930 pathogenic Breast-ovarian cancer, familial 2 2010-09-18 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000112966 SCV000145931 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000043880 SCV000587609 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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