ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4076C>T (p.Thr1359Ile) (rs878853578)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000772157 SCV000905266 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-01 criteria provided, single submitter clinical testing
Invitae RCV000230157 SCV000283227 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-04-29 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 1359 of the BRCA2 protein (p.Thr1359Ile). 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) and has not been reported in the literature in individuals with a BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 236861). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759613 SCV000889041 uncertain significance not provided 2018-04-19 criteria provided, single submitter clinical testing

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