ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.898G>A (p.Val300Ile) (rs878853616)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567574 SCV000661195 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Insufficient or conflicting evidence
Color RCV000567574 SCV000905245 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-21 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000504390 SCV000591717 likely benign not specified 2014-10-09 criteria provided, single submitter clinical testing
Invitae RCV000226110 SCV000283355 uncertain significance Hereditary breast and ovarian cancer syndrome 2015-12-16 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 300 of the BRCA2 protein (p.Val300Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual tested for Lynch syndrome (PMID: 25980754). The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. Moreover, 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. In summary, this is a novel missense change that is not predicted to affect protein function. However the evidence is insufficient at this time to prove that conclusively. It has been classified as a Variant of Uncertain Significance.

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