ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4389C>A (p.Tyr1463Ter) (rs80356997)

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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) RCV000112330 SCV000300113 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 RCV000048544 SCV000076557 pathogenic Hereditary breast and ovarian cancer syndrome 2016-05-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 1463 (p.Tyr1463*). It is expected to result in an absent or disrupted protein product. Truncating variants in BRCA1 are known to be pathogenic. This particular truncation has been reported in the literature in several individuals with a personal and/or family history of breast cancer (PMID: 23704984, 21993507, 12491487). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000162877 SCV000213364 pathogenic Hereditary cancer-predisposing syndrome 2017-01-17 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 RCV000236736 SCV000293203 pathogenic not provided 2017-11-07 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.4389C>A at the cDNA level and p.Tyr1463Ter (Y1463X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA1 4508C>A. The substitution creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAC>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been published as a pathogenic variant (Eng 2001, Andrulis 2002), observed in an individual with a HER2+ breast tumor (Larsen 2013) and we consider it to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000112330 SCV000296477 pathogenic Breast-ovarian cancer, familial 1 2016-05-27 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112330 SCV000325945 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000112330 SCV000677653 pathogenic Breast-ovarian cancer, familial 1 2017-05-17 criteria provided, single submitter clinical testing
Color RCV000162877 SCV000683178 pathogenic Hereditary cancer-predisposing syndrome 2017-05-15 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112330 SCV000145080 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000112330 SCV000297611 pathogenic Breast-ovarian cancer, familial 1 2013-09-04 no assertion criteria provided clinical testing

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