Table 4.

The pathogenicity scoring system for T4395C and T4363C mutations

Scoring criteria	T4395C mutation	Score	T4363C mutation	Score	Classification
More than one independent report	Yes	2	Yes	2
Evolutionary conservation of the base pair	No changes	2	2 changes	0
Variant heteroplasmy	No	0	No	0	≤6 points: neutral polymorphisms;
Segregation of the mutation with disease	Yes	2	Yes	2	7~10 points: possibly pathogenic;
Histochemical evidence of mitochondrial disease	Strong evidence	2	Strong evidence	2	≥11 points (including trans-mitochondrial cybrid studies): definitely pathogenic.
Biochemical defect in complex I, III or IV	No	0	No	0
Evidence of mutation segregation with biochemical defect from single-fiber studies	No	0	No	0
Mutant mt-tRNA steady-state level or evidence of pathogenicity in trans-mitochondrial cybrid studies	Strong evidence	5	Strong evidence	5
Maximum score		13		11	Definitely pathogenic