ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1386del (p.Thr464fs) (rs80357722)

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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) RCV000077489 SCV000299591 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000165641 SCV000216377 pathogenic Hereditary cancer-predisposing syndrome 2014-08-25 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 RCV000077489 SCV000296374 pathogenic Breast-ovarian cancer, familial 1 2015-08-13 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077489 SCV000325054 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077489 SCV000488223 pathogenic Breast-ovarian cancer, familial 1 2016-01-27 criteria provided, single submitter clinical testing
GeneDx RCV000479862 SCV000568427 pathogenic not provided 2017-05-02 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.1386delG at the cDNA level and p.Thr464ProfsX11 (T464PfsX11) at the protein level. The normal sequence, with the base that is deleted in brackets, is TTGG[delG]AAAAC. The deletion causes a frameshift which changes a Threonine to a Proline at codon 464, and creates a premature stop codon at position 11 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. Also published as BRCA1 1505delG, this variant has been observed in at least three individuals with breast cancer, one of whom also had a family history of breast and ovarian cancer (Pal 2008, Lee 2011, Malone 2006). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000496466 SCV000698856 pathogenic Hereditary breast and ovarian cancer syndrome 2016-10-18 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.1386delG (p.Thr464Profs) 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. The variant of interest was not observed in controls (ExAC, 1000 Gs, or ESP), and has been reported in multiple affected individuals via publications. In addition, multiple databases/clinical diagnostic laboratories cite the variant as "pathogenic." Therefore, the variant of interest has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077489 SCV000109287 pathogenic Breast-ovarian cancer, familial 1 2008-04-14 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077489 SCV000144075 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496466 SCV000587126 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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