NM_000249.4:c.342_347del (p.Ile115_Thr116del) is an in-frame deletion in exon 4 of MLH1. It is absent from all population databases (gnomAD v2.1, v4.1, gnomAD-Canada), meeting PM2_Supporting under the InSiGHT MLH1 VCEP framework.¹ Under the InSiGHT MLH1 VCEP v2.0.0, PVS1 is not applicable because this in-frame deletion does not introduce a premature termination codon and does not meet the VCEP criteria for nonsense, frameshift, or canonical splice variants.² No functional studies, tumor phenotype data, segregation data, or de novo observations were identified for this variant in any reviewed publication or database. Six papers were reviewed in full text; none mention NM_000249.4:c.342_347del.³ This variant has been reported in ClinVar as Uncertain Significance (1 clinical laboratory, criteria provided, single submitter). Under the InSiGHT MLH1 VCEP framework, PP5 is not applicable and this single submission does not constitute independent evidence for classification.⁴ With PM2_Supporting as the only met criterion and no benign criteria met, this variant remains a Variant of Uncertain Significance under the InSiGHT MLH1 VCEP classification rules. All other applicable criteria are either not met, not applicable by VCEP designation, or cannot be assessed due to absence of data.⁵