ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2213_2214dup (p.Lys739fs) (rs80357574)

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Total submissions: 6
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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) RCV000031038 SCV000323426 pathogenic Breast-ovarian cancer, familial 1 2016-10-18 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000167068 SCV000217896 pathogenic Hereditary cancer-predisposing syndrome 2017-07-12 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 RCV000031038 SCV000325294 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000657536 SCV000779272 pathogenic not provided 2018-05-03 criteria provided, single submitter clinical testing This duplication of two nucleotides in BRCA1 is denoted c.2213_2214dupTT at the cDNA level and p.Lys739LeufsX15 (K739LfsX15) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA1 2214_2215dupTT or 2332_2333dupTT. The normal sequence, with the bases that are duplicated in brackets, is ACAG[dupTT]AAAG. The duplication causes a frameshift, which changes a Lysine to a Leucine at codon 739 and creates a premature stop codon at position 15 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Invitae RCV001048511 SCV001212522 pathogenic Hereditary breast and ovarian cancer syndrome 2019-03-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys739Leufs*15) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in a family at increased risk of breast and/or ovarian cancer (PMID: 29446198). ClinVar contains an entry for this variant (Variation ID: 37457). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000031038 SCV000053632 pathogenic Breast-ovarian cancer, familial 1 2012-05-10 no assertion criteria provided clinical testing

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