Functional analysis of the novel mitochondrial tRNATrp and tRNASer(AGY) variants associated with type 2 diabetes mellitus

Table 1 Redefining the pathogenic roles of the m.A5514G and m.C12237T variants

Scoring criteria	m.A5514G variant	Score/20	m.C12237T variant	Score/20	Classification
More than one independent report	Yes	2	Yes	2	≤ 6 points: Neutral polymorphisms; 7-10 points: Possibly pathogenic; 11-13 points (not including evidence from single fiber, steady-state level, or trans-mitochondrial cybrid studies): Probably pathogenic; ≥ 11 points (including evidence from single fiber, steady-state level or trans-mitochondrial cybrid studies): Definitely pathogenic
Evolutionary conservation of the base pair	No changes	2	No changes	2
Variant heteroplasmy	No	0	No	0
Segregation of the mutation with disease	Yes	2	Yes	2
Biochemical defect in complex I, III, or IV	Yes	2	No	0
Evidence of mutation segregation with biochemical defect from single fiber studies	No evidence	0	No evidence	0
Mutant mt-tRNA steady-state level or evidence of pathogenicity in trans-mitochondrial cybrid studies	Strong evidence	5	No evidence	0
Maximum score	Definitely pathogenic	13	Neutral polymorphism	6