SCN9A and paroxysmal extreme pain disorder: This variant was classified as likely pathogenic by the American College of Medical Genetics and Genomics (ACMG) guidelines: PM1 (located in the highly conserved position in S4 of domain IV where PEPD-causing variants cluster), PM2_Supporting (absent from gnomAD v2.1.1 and v4.1.0), PM5 (different pathogenic missense substitution previously reported at the same residue, p.Leu1623Pro), PP3 (multiple in silico tools predict deleterious effect: REVEL 0.97, AlphaMissense 0.948), and PP4 (phenotype highly specific for SCN9A-related PEPD).