ClinVar Miner

Submissions for variant NM_177438.2(DICER1):c.3823A>G (p.Met1275Val) (rs751764482)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000561792 SCV000661898 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000225860 SCV000291667 uncertain significance DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2018-12-13 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 1275 of the DICER1 protein (p.Met1275Val). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs751764482, ExAC 0.006%). This variant has not been reported in the literature in individuals with DICER1-related disease. ClinVar contains an entry for this variant (Variation ID: 242092). 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 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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