The m.13513G>A (p. D393N) variant in MT-ND5 was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel as part of the variant pilot for mitochondrial DNA variant specifications (McCormick et al., 2020; PMID: 32906214). This variant has been reported in >16 individuals with primary mitochondrial disease with onset typically in childhood with some reports of onset in adolescence who had features variably consistent with Leigh syndrome, MELAS and MELAS-like, and/or mitochondrial encephalopathy (PS4; PMID: 25681084; PMID: 27344355; PMID: 30128709; PMID: 12624137; PMID: 14520659; PMID: 17400793; PMID: 18495510). This variant has been identified as a de novo occurrence in at least 5 probands with primary mitochondrial disease (PM6_strong; PMID: 27344355; PMID: 17400793; PMID: 18495510). This variant heteroplasmy level segregated with severity in 6 families where healthy mothers were found to have the variant at low heteroplasmy levels (PP1_moderate; PMID: 25681084; PMID: 12624137; PMID: 14520659). Another variant at this amino acid position leading to a different amino acid change is classified as pathogenic by mitomap.org and ClinVar – m.13514A>G (p.D393G; PM5). The computational predictor APOGEE gives a consensus rating of pathogenic with a score of 0.97 (Min=0, Max=1), which predicts a damaging effect on gene function (PP3). In summary, this variant meets criteria to be classified as pathogenic for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD U24 Mitochondrial Disease Variant Curation Expert Panel as of August 20, 2020. Mitochondrial DNA-specific ACMG/AMP criteria applied: PS4, PM6_strong, PM5, PP1_moderate, PP3).