NM_000314.8:c.348del predicts PTEN p.(Asp116GlufsTer18), a frameshift expected to truncate the protein early in exon 5. The PTEN PVS1 decision tree assigns PVS1 to frameshift variants in NM_000314.8 when the stop/disruption occurs at or 5' to p.D375 (c.1121); this variant truncates at p.Asp116fs, which is well upstream of that threshold and is consistent with loss of function.¹ The variant is absent from gnomAD v2.1 and gnomAD v4.1, and the PTEN specification applies PM2 at Supporting strength for variants with allele frequency below 0.00001, with a subpopulation threshold below 0.00002 when multiple alleles are present.² No PTEN-specific final classification framework was retrieved, so the generic ACMG/AMP combination rules were used as fallback; with PVS1 and PM2_Supporting alone, this evidence set does not reach a defined pathogenic or likely pathogenic combination under those rules, and the variant is therefore classified as a variant of uncertain significance pending human review.³