ClinVar Miner

Submissions for variant NM_177438.2(DICER1):c.1004A>G (p.His335Arg) (rs1060503602)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000471033 SCV000553528 uncertain significance DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2017-04-07 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 335 of the DICER1 protein (p.His335Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a DICER1-related disease. 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 mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a novel missense change with uncertain impact on protein function and mRNA splicing. It has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000573917 SCV000662006 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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