PM1_Moderate is met: p.Glu1813Gln affects codon p.E1813, a metal ion-binding residue in the RNase IIIb domain explicitly listed in the DICER1 VCEP PM1 moderate rule. Crystal structure data confirm E1813 coordinates the catalytic Mg-1 ion.¹ PM2_Supporting is met: NM_177438.3:c.5437G>C is absent from gnomAD v2.1, v4.1, and gnomAD-Canada (0 alleles across all populations), satisfying the VCEP threshold of AF < 0.000005.² PP3_Supporting is met: REVEL score is 0.859, meeting the DICER1 VCEP threshold of ≥ 0.750 for missense variants.³ PVS1 is not applicable: this is a missense variant and does not fall into the VCEP-defined null-variant buckets (nonsense, frameshift, canonical splice).⁴ PS1 is not met: no comparator variant encoding p.Glu1813Gln has been classified as Pathogenic by the DICER1 VCEP.⁵ PS3 is not met: no variant-specific functional assay has been performed for p.Glu1813Gln. The cleavage assay in PMID:22187960 tested D1709N, D1709E, and E1705K but not E1813Q.⁶ PM5 is not applicable per VCEP rule: PM5 cannot be applied in combination with PM1, and PM1_Moderate is met.⁷ PP4 is not applicable per VCEP rule: the germline variant itself is a missense in one of the seven RNase IIIb hotspot codons (p.E1813).⁸ With PM1_Moderate (+2), PM2_Supporting (+1), and PP3_Supporting (+1), the total Tavtigian point score is +4, which falls in the DICER1 VCEP Uncertain Significance range (-1 to +5).⁹