ClinVar Miner

Submissions for variant NM_177438.2(DICER1):c.1124C>G (p.Pro375Arg) (rs148758903)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000231396 SCV000291603 uncertain significance DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2019-01-05 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 375 of the DICER1 protein (p.Pro375Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is present in population databases (rs148758903, ExAC 0.05%), 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: 242032). 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Illumina Clinical Services Laboratory,Illumina RCV000263539 SCV000389766 likely benign Pleuropulmonary blastoma 2016-06-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000570796 SCV000661811 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761116 SCV000891032 uncertain significance Neuroblastoma 2016-12-27 no assertion criteria provided clinical testing

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