ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5147A>G (p.Tyr1716Cys) (rs587782456)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131529 SCV000186523 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-15 criteria provided, single submitter clinical testing Insufficient evidence
GeneDx RCV000486773 SCV000564748 uncertain significance not provided 2018-11-15 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.5147A>G at the cDNA level, p.Tyr1716Cys (Y1716C) at the protein level, and results in the change of a Tyrosine to a Cysteine (TAT>TGT). Using alternate nomenclature, this variant would be defined as BRCA1 5266A>G. This variant has been observed in at least one individual referred for BRCA1 testing (Judkins 2005). BRCA1 Tyr1716Cys was not observed in large population cohorts (Lek 2016). This variant is located in Located in the BRCT 1 domain and a region known to interact with multiple other proteins (UniProt, Paul 2014). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRCA1 Tyr1716Cys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000131529 SCV000688539 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-27 criteria provided, single submitter clinical testing
Invitae RCV000637366 SCV000758822 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-04-25 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 1716 of the BRCA1 protein (p.Tyr1716Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 142424). 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 disruptive, 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.
Brotman Baty Institute,University of Washington RCV001077662 SCV001243621 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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