ClinVar Miner

Submissions for variant NM_177438.2(DICER1):c.4923T>G (p.Cys1641Trp) (rs587778231)

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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 RCV000571868 SCV000661854 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Fulgent Genetics,Fulgent Genetics RCV000765191 SCV000896426 uncertain significance Goiter, multinodular 1, with or without Sertoli-Leydig cell tumors; Rhabdomyosarcoma, embryonal, 2; DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2018-10-31 criteria provided, single submitter clinical testing
ITMI RCV000120642 SCV000084803 not provided not specified 2013-09-19 no assertion provided reference population
Invitae RCV000232310 SCV000291703 uncertain significance DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2018-12-05 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tryptophan at codon 1641 of the DICER1 protein (p.Cys1641Trp). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tryptophan. This variant is present in population databases (rs587778231, ExAC 0.05%) but has not been reported in the literature in individuals with a DICER1-related disease. ClinVar contains an entry for this variant (Variation ID: 133973). 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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