ClinVar Miner

Submissions for variant NM_177438.2(DICER1):c.4945A>G (p.Met1649Val) (rs146715213)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000465635 SCV000553590 uncertain significance DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 1649 of the DICER1 protein (p.Met1649Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs146715213, ExAC 0.01%). This variant has not been reported in the literature in individuals with DICER1-related disease. ClinVar contains an entry for this variant (Variation ID: 412129). 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.
Ambry Genetics RCV001023306 SCV001185163 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-29 criteria provided, single submitter clinical testing Insufficient evidence
Illumina Clinical Services Laboratory,Illumina RCV000465635 SCV001277791 uncertain significance DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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