The c.1105C>T variant in DNM2 is a missense variant predicted to cause substitution of arginine by tryptophan at amino acid 369 (p.Arg369Trp). The highest population minor allele frequency in gnomAD v4.1 is 0.00001335 (1/74912 alleles) in the African/African American population, which is lower than the ClinGen Congenital Myopathies VCEP threshold for PM2_Supporting, meeting this criterion (PM2_Supporting). DNM2, in which the variant was identified, is defined by the ClinGen Congenital Myopathies VCEP as a gene that has a low rate of benign missense variation and where pathogenic missense variants are a common mechanism of disease (PP2). The computational predictor REVEL gives a score of 0.683, which is neither above nor below the thresholds predicting a damaging or benign impact on RYR1 function. This variant has been reported in at least 11 probands from 6 families meeting phenotypic criteria distal muscular weakness and ptosis, which is highly specific for centronuclear myopathy (PS4; PMIDs: 16227997, 20817456, 22613877, 25492887, 25501959, 28676641). The variant has been reported to segregate with centronuclear myopathy in 5 affected family members from 2 families (PP1_Strong; PMIDs: 16227997, 22613877). Two different missense variants (c.1106G>T, p.Arg369Leu; p.Arg369Gln, c.1106G>A) in the same codon have been classified as likely pathogenic and pathogenic, respectively, for autosomal dominant centronuclear myopathy by the ClinGen Congenital Myopathies VCEP (and autosomal dominant Charcot-Marie-Tooth disease by the ClinGen Charcot-Marie-Tooth disease VCEP) (PM5). This variant has been identified as a de novo occurrence with unconfirmed parental relationships in 1 individual with centronuclear myopathy (PM6; PMIDs: 16227997). A cell culture of human myoblasts from quadriceps showed impaired actin development, indicating that this variant impacts protein function (PMID: 28676641; PS3_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for autosomal dominant centronuclear myopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen Congenital Myopathies VCEP: PS4, PP1_Strong, PM5, PM6, PM2_Supporting, PP2, PS3_Supporting. (ClinGen Congenital Myopathies VCEP specifications version 1; 8/7/24)