Table 3. Structural classification and pathogenic prediction of mutations in the mtDNA complex III and IV genes (mt-cyb and mt-co1-3, respectively) reported with human disease associations but without known biochemical effects.

						Predictions
Human subunit (Gene)	Human residue (Nucleotide)	Human disease	Reference	Hetero−/Homo-plasmy	Class	SIFT	Polyphen	Mutation Assessor	3D Modeling
MT-CYB(mt-cyb)	N32S (A14841G)	LHON helper mutation	[82]	Het	3	Affect	Pathogenic	High	Pathogenic
MT-CO1(mt-co1)	V374M (G7023A)	MELAS-like syndrome	[83]	Het	2	Affect	Pathogenic	High	Pathogenic
	V380I (G7041A)*	Prostate Cancer	[84]	Homo	2	Affect	Pathogenic	High	Pathogenic
	A120T (G6261A)*	Prostate Cancer/LHON	[58], [59], [84]	Homo	4	Tolerated	Benign	Neutral	Pathogenic
	I419V (A7158G)*	Prostate Cancer	[19]	Homo	4	Tolerated	Benign	Neutral	Pathogenic
	V193I (G6480A)*	Prostate Cancer	[19], [20], [85]	Homo	4	Tolerated	Benign	Neutral	Pathogenic
	M117T (T6253C)*	Prostate Cancer	[19], [58]	Homo	4	Tolerated	Benign	Medium	Pathogenic
MT-CO2(mt-co2)	E18K (G7637A)*	PD risk factor	[86]	Het/Homo	4	Affect	Pathogenic	High	Yes
	D92N (G7859A)*	Progressive Encephalomyopathy	[87]	Homo	4	Tolerated	Benign	Neutral	Pathogenic
	L95F (C7868T)	LHON	[82]	Homo	4	Affect	Benign	Medium	Pathogenic

Abbreviations: LHON – Leber Hereditary Optic Neuropathy,

^*also reported as polymorphism,

^$reported as somatic (rather than inherited) mutation, Het – reported as a mixture of wild-type and mutated mtDNAs in affected patients, Hom – reported as mutated mtDNAs only in patients, Het/Homo – reported as heteroplasmy in some patients but or homoplasmy in others.