ClinVar Miner

Submissions for variant NM_177438.2(DICER1):c.4283T>A (p.Met1428Lys) (rs996633792)

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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 RCV000562615 SCV000669348 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000459122 SCV000553578 uncertain significance DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2018-12-16 criteria provided, single submitter clinical testing This sequence change replaces methionine with lysine at codon 1428 of the DICER1 protein (p.Met1428Lys). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a DICER1-related disease. ClinVar contains an entry for this variant (Variation ID: 412118). 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, this variant has uncertain impact on DICER1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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