Table 2

MTND gene mutations analysed with the complex I pathogenicity scoring system

Gene	Mutation	Status*	Amino acid substitution	Disease association	Score	MITOMAP status
Fifty MTND gene mutations listed on the MITOMAP database⁹ or recently reported¹⁰ were given a pathogenicity score (maximum score of 40) according to the criteria described in the Methods and in table 1. The acronyms and abbreviations used to describe the clinical and disease presentations not used in the text are as given on the MITOMAP database.
*Status refers to whether a mutation is described as heteroplasmic (Het) or homoplasmic (Hom) on MITOMAP.
AD, Alzheimer’s disease; CPEO, chronic progressive external ophthalmoplegia; DM, diabetes mellitus; ESOC, epilepsy, stroke-like episodes, optic atrophy and cognitive decline; LDYT, LHON and dystonia; LHON, Leber hereditary optic neuropathy; MELAS, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes; NIDDM, non-insulin dependent diabetes mellitus; PD, Parkinson’s disease.
MTND1	3308T→C	Het	M→T	MELAS	5	Polymorphism
	3316G→A	Hom	A→T	NIDDM, LHON	5	Unclear
	3394T→C	Hom	Y→H	LHON, NIDDM	3	Unclear
	3397A→G	Hom	M→V	AD/PD	5	Provisional
	3460G→A	Hom/Het	A→T	LHON	39	Confirmed
	3496G→T	Hom	A→S	AD/PD and LHON	2	Provisional/secondary
	3497C→T	Hom	A→V	LHON	0	Provisional/secondary
	3635G→A	Hom	S→N	LHON	9	Provisional
	3697G→A	Het	G→S	MELAS	32	Reference 10
	3796A→G	Het	T→A	Adult onset dystonia	13	Provisional
	3946G→A	Het	E→K	MELAS	32	Reference 10
	3949T→C	Het	Y→H	MELAS	32	Reference 10
	4136A→G	Hom	Y→C	LHON	6	Provisional
	4160T→C	Hom	L→P	LHON	5	Provisional
	4171C→A	Hom/Het	L→M	LHON	17	Provisional
	4216T→C	Hom	Y→H	LHON	5	Confirmed
MTND2	4640G→A	Hom	I→M	LHON	12	Provisional
	4917A→G	Hom	N→D	LHON	0	Confirmed
	5244G→A	Het	G→S	LHON	9	Provisional
	5460G→A	Hom/Het	A→T	AD	0	Polymorphism
	5460G→T	Hom/Het	A→S	AD	7	Provisional
MTND3	10158T→C	Het	S→P	Leigh	33	Confirmed
	10191T→C	Het	S→P	ESOC/Leigh-like	32	Confirmed
MTND4L	10663T→C	Hom	V→A	LHON	31	Provisional
MTND4	11084A→G	Hom/Het	T→A	MELAS	6	Polymorphism
	11232T→C	Het	L→P	CPEO	24	Provisional
	11696G→A	Het	V→I	LHON	17	Provisional
	11777C→A	Het	R→S	Leigh	32	Provisional
	11778G→A	Hom/Het	R→H	LHON	34	Confirmed
	11832G→A	Het	W→Ter	Exercise intolerance	33	Provisional
	12026A→G	Hom	I→V	DM	2	Provisional
MTND5	12706T→C	Het	F→L	Leigh	30	Confirmed
	12770A→G	Het	E→G	MELAS	17	Provisional
	13045A→C	Het	M→L	MELAS/LHON/Leigh overlap syndrome	25	Provisional
	13084A→T	Het	S→C	MELAS/Leigh	26	Provisional
	13513G→A	Het	D→N	MELAS/Leigh	39	Confirmed
	13514A→G	Het	D→G	MELAS	37	Confirmed
	13528A→G	Hom	T→A	LHON-like	1	Provisional
	13708G→A	Hom	A→T	LHON	7	Unclear
	13730G→A	Het	G→E	LHON	9	Provisional
MTND6	14453G→A	Het	A→V	MELAS	19	Provisional
	14459G→A	Hom/Het	A→V	LDYT/Leigh	37	Confirmed
	14482C→A	Hom/Het	M→I	LHON	10	Provisional
	14482C→G	Hom/Het	M→I	LHON	17	Confirmed
	14484T→C	Hom/Het	M→V	LHON	37	Confirmed
	14487T→C	Het	M→V	Leigh/dystonia	39	Confirmed
	14495A→G	Het	L→S	LHON	17	Provisional
	14498T→C	Hom/Het	Y→C	LHON	17	Provisional
	14568C→T	Hom	G→S	LHON	7	Provisional
	14596A→T	Hom	I→M	LHON	19	Provisional