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Table 5.

Complex IV variants

Disease/clinical features	Variant	Subunit	AA change	Age^a	% VAF				Complex IV		Reference
Disease/clinical features	Variant	Subunit	AA change	Age^a	Muscle	Blood	Fibroblasts	Other	Residual activity, %	Protein levels	Reference
Epilepsia partialis continua	6489C > A	MT-CO1	Leu196Ileu	17 yr	95	30			74, muscle		(Varlamov et al. 2002)
Rhabdomyolysis, myopathy	6708G > A	MT-CO1	Gly269X	30 yr	81–89	<1			21, muscle^b	↓	(Kollberg et al. 2005)
Multisystem mitochondrial disease	6930G > A	MT-CO1	Gly343X	21 yr	75	27		35, 65, cybrids 33, myoblasts	10, muscle 50, cybrids with vaf of 35% 25, cybrids with vaf of 65%	↓	(Bruno et al. 1999)
EXIT with mild intellectual disability	6955G > A	MT-CO1	Gly351Asp	13 yr	100				15, muscle	↓	(Herrero-Martin et al. 2008)
McArdle's syndrome	7444G > A	MT-CO1	X514Lys	57 yr	100				35, muscle		(Aguilera Garcia-Lozano et al. 2001)
Mitochondrial encephalomyopathy	7587T > C	MT-CO2	Met1Thr	57 yr	67	<1	52		38, muscle	↓	(Clark et al. 1999)
Proximal myopathy and lactic acidosis	7671T > A	MT-CO2	Met29Lys	14 yr	90	5			6, muscle	↓	(Rahman et al. 1999)
Multisystem mitochondrial disease	7896G > A	MT-CO2	Trp104X	3 yr	76	67	60		13, muscle	↓	(Campos et al. 2001)
Multisystem mitochondrial disease	7970G > T	MT-CO2	E129X	35 yr	90				3, muscle	↓	(Horváth et al. 2005)
Myopathy, EXIT, lactic acidosis, lipidosis, ragged red fibers	9379G > A	MT-CO3	W58X	14 yr	93			<1, hair	1, muscle	↓	(Horvath et al. 2002)
MELAS	9396G > A	MT-CO3	Glu64Lys	11 yr	94	39	91	100, urinary sediment 74, saliva 77, fingernails 95, cybrids	78, muscle 78, cybrids		(Xu et al. 2021)
MELAS	9553G > A	MT-CO3	Trp116X	47 yr	89			13, oral epithelium	59, muscle	↓	(Wang et al. 2021)
Rhabdomyolysis	9559delC	MT-CO3	Frameshift	27 yr	58				38, muscle^c	↓	(Marotta et al. 2011)
EXIT, rhabdomyolysis	9789T > C	MT-CO3	Ser195Pro	23 yr	50	<1		<1, myoblasts	10, muscle	↓	(Horváth et al. 2005)
Mitochondrial encephalomyopathy	9952G > A	MT-CO3	Trp248X	36 yr	57				17, muscle	↓	(Hanna et al. 1998)
MELAS	9957T > C	MT-CO3	Phe251Leu	7 yr	81	60			79, muscle	Similar levels as referent	(Manfredi et al. 1995)

[i] ^aAge of the patient at which the VAF and complex I activity were measured.

[ii] ^bNormalized to protein.

[iii] ^cNormalized to complex II activity.

[iv] (AA) Amino acid; (VAF) variant allele frequency; (COX) cytochrome c oxidase; (EXIT) exercise intolerance; and (MELAS) mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes.