ClinVar Miner

Submissions for variant NM_177438.2(DICER1):c.1381A>G (p.Ile461Val) (rs141163928)

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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 RCV000566185 SCV000661833 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Illumina Clinical Services Laboratory,Illumina RCV000331637 SCV000389764 likely benign Pleuropulmonary blastoma 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000229670 SCV000291608 uncertain significance DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2018-06-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 461 of the DICER1 protein (p.Ile461Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs141163928, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with DICER1-related disease. ClinVar contains an entry for this variant (Variation ID: 242037). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
PreventionGenetics RCV000851438 SCV000993721 uncertain significance not provided 2018-12-04 criteria provided, single submitter clinical testing

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