Table 4 of
Bosley, Mol Vis 2007;
13:1516-1528.Table 4 of
Bosley, Mol Vis 2007;
13:1516-1528.
Table 4. Non-synonymous mitochondrial DNA sequence changes detected in control subject
This table assesses each nucleotide change in controls not previously found to be haplogroup-specific polymorphism as described in Methods. "Transversion" is 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), and "Transition" is 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 (%)" represents percent of controls with this nucleotide substitution. "Heteroplasmy (%)" represents percent of mutant DNA present. "NA" represents not applicable because the nucleotide change was always found in homoplasmic state. To determine novelty, previous reports of sequence variants were found in the MITOMAP database, the human mitochondrial Genome database, GenBank, and Medline listed publications. Interspecies conservation was assessed using PolyPhen 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" indicates nucleotide change will alter protein secondary structure; "No" indicates change will not alter secondary structure. PolyPhen prediction of pathogenicity was assessed utilizing 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. The Sorting Intolerant from Tolerant website (SIFT) returns predictions for which amino acid substitutions will affect protein function. "Yes" means an amino acid change is predicted to affect protein function, while "No" means the amino acid change is not predicted to affect protein function. Summary: A sequence variant was considered potentially pathologic if it satisfied all the following conditions, where possible: it changed a moderately or highly conserved amino acid; Protean predicted an alteration of protein structure; it was predicted by SIFT to have an effect on protein function; and it was assessed as possibly or probably pathogenic by PolyPhen.
Base
Nucleotide AA substitution Controls Heteroplasmy Interspecies
substitution change Location type (%) (%) Novel conservation Protean Polyphen SIFT Summary
------------ ------ -------------------- ------------ -------- ------------ ----- ------------ ------- -------- ---- --------------
4012 A>G T236A Functional domain of Transition 0.6 NA No High Yes Benign No Non-Pathologic
ND1 gene
4013 C>G T236S Functional domain of Transversion 0.6 NA No High Yes Benign No Non-Pathologic
ND1 gene
4734 A>G T89A Outside the TM Transition 0.6 NA No Low Yes Benign No Non-Pathologic
domain of ND2 gene
4904 C>A I145M Outside the TM Transversion 0.6 NA No Low No Benign No Non-Pathologic
domain of ND2 gene
5263 C>T A265V Outside the TM Transition 4.4 NA No Low Yes Benign Yes Non-Pathologic
domain of ND2 gene
5913 G>A D4N Outside the TM Transition 3.1 NA No Low No Benign No Non-Pathologic
domain of COI gene
6040 A>G N46S Outside the TM Transition 1.9 NA No Low No Benign No Non-Pathologic
domain of COI gene
7278 T>C F459L Outside the TM Transition 0.6 NA No High No Benign No Non-Pathologic
domain of COI gene
7369 C>G S489C Outside the TM Transversion 0.6 NA No Moderate Yes Benign NA Non-Pathologic
domain of COI gene
7646 A>C I21L Outside the TM Transversion 0.6 NA No Low No Benign No Non-Pathologic
domain of COII gene
8587 G>A V21M TM domain of ATPase Transition 0.6 NA No Low No Benign No Non-Pathologic
6 gene
9104 T>C F193S Outside the TM Transition 0.6 NA Yes Moderate No Benign Yes Non-Pathologic
domain of ATPase 6
gene
9300 G>A A32T TM domain of COIII Transition 3.1 NA No Moderate Yes Benign Yes Non-Pathologic
gene
9337 T>C M44T TM domain of COIII Transition 3.8 NA No Low Yes Benign No Non-Pathologic
gene
9539 A>T Q111H Outside TM domain of Transversion 1.3 NA No Low Yes Benign No Non-Pathologic
COIII gene
9667 A>G N154S Outside TM domain of Transition 6.9 NA No Low No Benign No Non-Pathologic
COIII gene
9822 C>T L206F TM domain of COIII Transition 1.3 NA No High No Benign Yes Non-Pathologic
gene
9966 G>A V254I TM domain of COIII Transition 0.6 NA No Moderate No Benign No Non-Pathologic
gene
10079 A>C L7F TM domain of ND3 Transversion 1.3 NA No Low No Benign No Non-Pathologic
gene
13811 C>G A492G TM domain of ND5 Transversion 0.6 NA No Low Yes Benign No Non-Pathologic
gene
14562 C>T V38I TM domain of ND6 Transition 0.6 NA No High No Benign No Non-Pathologic
gene
14582 A>G V31A TM domain of ND6 Transition 8.2 NA No Low No Benign No Non-Pathologic
gene
14831 G>A A29T Outside the TM Transition 1.9 NA No Low No Benign No Non-Pathologic
domain of CYTB gene
14862 C>T A39V TM domain of CYTB Transition 0.6 NA No Low Yes Benign No Non-Pathologic
gene
15267 C>A T174N Outside TM domain of Transversion 0.6 NA No High Yes Benign Yes Non-Pathologic
CYTB gene
15617 G>A V291I TM domain of CYTB Transition 1.3 NA No High No Benign Yes Non-Pathologic
gene
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