ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3845A>T (p.Glu1282Val) (rs80357217)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000212177 SCV000883468 uncertain significance not provided 2017-11-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162771 SCV000213248 likely benign Hereditary cancer-predisposing syndrome 2017-02-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Intact protein function observed in appropriate functional assay(s),Other data supporting benign classification,Rarity in general population databases (dbsnp, esp, 1000 genomes)
Breast Cancer Information Core (BIC) (BRCA1) RCV000112199 SCV000144896 uncertain significance Breast-ovarian cancer, familial 1 2003-12-23 no assertion criteria provided clinical testing
Color RCV000162771 SCV000911508 likely benign Hereditary cancer-predisposing syndrome 2017-02-07 criteria provided, single submitter clinical testing
Counsyl RCV000112199 SCV000488120 uncertain significance Breast-ovarian cancer, familial 1 2016-01-07 criteria provided, single submitter clinical testing
GeneDx RCV000212177 SCV000210158 uncertain significance not provided 2017-12-21 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3845A>T at the cDNA level, p.Glu1282Val (E1282V) at the protein level, and results in the change of a Glutamic Acid to a Valine (GAA>GTA). Using alternate nomenclature, this variant would be defined as BRCA1 3964A>T. A functional study by Bouwman et al. (2013) classified this as a neutral variant based on restoration of proliferation in BRCA1-deficient mouse embryonic stem cells as well as lack of significant sensitivity to cisplatin exposure. However, a subset of splicing models predict the creation of a cryptic splice site upstream of a canonical donor site which may or may not cause abnormal gene splicing. BRCA1 Glu1282Val was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Glutamic Acid and Valine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Glu1282Val is located in the SCD domain and a region known to interact with multiple other proteins (Narod 2004, Paul 2014). Protein-based in-silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available information, it is unclear whether BRCA1 Glu1282Val is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000048355 SCV000076368 likely benign Hereditary breast and ovarian cancer syndrome 2017-11-29 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000112199 SCV000296462 uncertain significance Breast-ovarian cancer, familial 1 2016-05-02 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000112199 SCV000189340 likely benign Breast-ovarian cancer, familial 1 2012-03-16 no assertion criteria provided clinical testing

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