NM_005228.4:c.2317_2318insCCCACCCCA (p.His773delinsProHisProAsn) is an in-frame insertion in exon 20 of EGFR, within the tyrosine kinase domain. This variant is absent from population databases including gnomAD v2.1, v4.1, and gnomAD-Canada (PM2_supporting).¹ The in-frame insertion in a non-repeat functional domain meets PM4 at moderate strength. No variant-specific functional studies were identified in five reviewed publications; OncoKB classifies the variant as Likely Oncogenic in a somatic context, but this does not independently satisfy germline PS3.² The variant is absent from ClinVar; no expert panel or submitter classification is available.³ The variant is not in a statistically significant mutational hotspot per Cancer Hotspots analysis, and in silico splicing predictors (SpliceAI max delta 0.08) do not indicate a splice effect.⁴ Overall, 1 moderate criterion (PM4) and 1 supporting criterion (PM2) are met. This does not reach the threshold for Likely Pathogenic (requires ≥2 moderate + ≥2 supporting, ≥3 moderate, or 1 strong + ≥1 moderate). The variant is classified as a Variant of Uncertain Significance (VUS) under generic ACMG/AMP 2015 criteria.⁵