ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4670C>T (p.Thr1557Ile) (rs80358698)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000565644 SCV000668613 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735554 SCV000863692 uncertain significance Breast and/or ovarian cancer 2008-03-03 no assertion criteria provided clinical testing
Invitae RCV000233033 SCV000283244 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-05-06 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 1557 of the BRCA2 protein (p.Thr1557Ile). The threonine residue is moderately 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 not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 236870). 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 C15". 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 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.

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