ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4649C>T (p.Thr1550Ile) (rs80357076)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129109 SCV000183820 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Breast Cancer Information Core (BIC) (BRCA1) RCV000112373 SCV000145139 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000129109 SCV000688507 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-23 criteria provided, single submitter clinical testing
Counsyl RCV000112373 SCV000488717 uncertain significance Breast-ovarian cancer, familial 1 2016-06-01 criteria provided, single submitter clinical testing
GeneDx RCV000048618 SCV000210182 uncertain significance not provided 2018-04-24 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.4649C>T at the cDNA level, p.Thr1550Ile (T1550I) at the protein level, and results in the change of a Threonine to an Isoleucine (ACA>ATA). This variant is also defined as BRCA1 4768C>T using alternate nomenclature, and BRCA1 T1571I using an alternate transcript. This variant has been observed in at least one individual with hyperdiploid acute lymphoblastic leukemia (Zhang 2015). Functional interrogation of this variant by in vitro transcription activation assay demonstrated activity exceeding wild type (Woods 2016). BRCA1 Thr1550Ile was not observed in large population cohorts (Lek 2016). This variant is located in a region known to interact with multiple proteins (Paul 2014). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA1 Thr1550Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000129109 SCV000679698 uncertain significance Hereditary cancer-predisposing syndrome 2017-07-12 criteria provided, single submitter clinical testing
Invitae RCV000195394 SCV000076631 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-09-04 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 1550 of the BRCA1 protein (p.Thr1550Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with acute lymphoblastic leukemia (ALL), and is also known as T1571I in the literature (PMID: 26580448). This variant has been reported in affected patients in the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 55251). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000112373 SCV000296308 uncertain significance Breast-ovarian cancer, familial 1 2016-04-15 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.