Table 2 of
Abu-Amero, Mol Vis 2008;
Table 2. Nonsynonymous mtDNA sequence changes detected in PEG patients
In the "Base substitution type" column, Transversion=A mutation in which a purine/pyrimidine replaces a pyrimidine/purine base pair or vice versa (G:C>T:A or C:G, or A:T>T:A or C:G); Transition=A mutation in which a purine/pyrimidine base pair is replaced with a base pair in the same purine/pyrimidine relationship (A:T>G:C or C:G>T:A). Controls (%)=percent of controls with this nucleotide substitution. Previous reports of sequence variants were found in the Human Mitochondrial Genome Database (MITOMAP database), GenBank, and Medline listed publications. Interspecies conservation was assessed using the Polymorphism Phenotyping (PolyPhen) database, which determines interspecies conservation for an altered amino acid by performing alignment with all available amino acid sequences for other species, and the Mamit-tRNA website when necessary. Protean predicts and displays secondary structural characteristics. "Yes"=nucleotide change will alter protein secondary structure; "No"=change will not alter secondary structure. PolyPhen prediction of pathogenicity was assessed using the PolyPhen database. "Probably damaging" constitutes a high confidence of affecting protein function or structure. "Possibly damaging" reflects a likelihood of affecting protein function or structure, while "Benign" changes most likely lack phenotypic effect. "Unknown" means that PolyPhen could not make a prediction due to lack of data. None of these nucleotide changes was heteroplasmic. Summary; see Prediction of Pathogenicity in Methods. TM= transmembrane. N/A=not applicable because the database is not designed to predict this type of sequence change. Reported haplogroup specific NS sequence changes were excluded from Table 2 and further analysis.
Base Nucleotide AA substitution Controls Interspecies substitution change Location type (%) Novel conservation Protean PolyPhen Summary ------------ ------ ---------- ------------ -------- ----- ------------ ------- -------- -------------- 3833 T>A L176Q TM domain Transversion 0 Yes Moderate Yes Probably Pathologic of ND1 damaging gene 4363 T>C N/A Anticodon Transition 0.62 No High N/A Unknown Non-pathologic loop of tRNA glutamine 4385 A>G N/A In the T?C Transition 0.62 No High N/A Unknown Non-Pathologic domain of the tRNA glutamine 4648 T>C F60S Outside Transition 0 Yes High Yes Probably Pathologic the TM damaging domain of ND2 gene 5182 C>T T238M Outside Transition 0 Yes Low No Benign Non-Pathologic the TM domain of ND2 gene 5843 A>G N/A In the Transition 1.2 No High N/A Unknown Non-pathologic D-loop of tRNA tyrosine 6546 C>T L215F Outside Transition 0.62 No High No Benign Non-pathologic the TM domain of COI gene 7877 A>C K98Q Outside Transversion 0 Yes High No Probably Pathologic the TM damaging domain of COII gene 9103 T>C F193L Outside Transition 1.2 No Moderate No Benign Non-pathologic the TM domain of ATPase 6 gene 9438 G>A G78S Outside Transition 3.14 No High No Benign Non-pathologic the TM domain of COIII gene 11337 A>G N193S TM domain Transition 1.9 No Low No Benign Non-pathologic of ND4 gene 12841 A>G I169V Outside Transition 3.1 No Low No Benign Non-pathologic the TM domain of ND5 gene 13813 G>A V493I TM domain Transition 1.9 No High No Benign Non-pathologic of ND5 gene