ClinVar

Description

The m.12544A>G (p.T70A) 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). There have been no affected individuals reported in the medical literature to our knowledge. There are no large families reported in the medical literature to consider for evidence of segregation. There are two occurrences in the GenBank sequences queried through MITOMAP on 6/29/2020 (1 individual from haplogroup U2e and 1 from L2a). In silico tools (APOGEE) predict this variant to be neutral (score of 0.39, BP4). There are no cybrid or single fiber studies reported on this variant. In summary, this variant meets criteria to be classified as uncertain significance 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: BP4.