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Table 6.

Complex V variants

Disease/clinical features	Variant	Subunit	AA change	Age^a	% VAF				Complex V		Reference
Disease/clinical features	Variant	Subunit	AA change	Age^a	Muscle	Blood	Fibroblasts	Other	Residual activity, %	Protein levels	Reference
Hypertrophic cardiomyopathy and neuropathy	8529G > A	MT-ATP8	Trp55X	16 yr	90		90	100, cybrids	17, muscle^b 21, fibroblasts^b 16, cybrids^b	↓	(Jonckheere et al. 2008)
MILS	8993T > C	MT-ATP6	Leu156Pro	5 yr	94	94	98		81, fibroblasts		(Santorelli et al. 1996)
NARP	8993T > C	MT-ATP6	Leu156Pro	13 yr	94	94	98		86, fibroblasts		(Santorelli et al. 1996)
Spinocerebellar ataxia/Leigh syndrome	8993T > C	MT-ATP6	Leu156Pro	23 yr	94	94	98		32, fibroblasts		(Santorelli et al. 1996)
MILS	8993T > C	MT-ATP6	Leu156Pro	4 yr	94	94	98		10, fibroblasts		(Santorelli et al. 1996)
Mitochondrial encephalomyopathy	8993T > C	MT-ATP6	Leu156Pro		>95	>95			41, muscle	↓	(Morava et al. 2006)
Mitochondrial encephalomyopathy	8993T > C	MT-ATP6	Leu156Pro		>95	>95			49, muscle	↓	(Morava et al. 2006)
Mitochondrial encephalomyopathy	8993T > C	MT-ATP6	Leu156Pro		>95	>95			52, muscle	↓	(Morava et al. 2006)
Mitochondrial encephalomyopathy	8993T > C	MT-ATP6	Leu156Pro		>95	>95			29, muscle	↓	(Morava et al. 2006)
Mitochondrial encephalomyopathy	8993T > C	MT-ATP6	Leu156Pro		>95	>95			25, muscle	↓	(Morava et al. 2006)
Leigh syndrome	8993T > G	MT-ATP6	Leu156Arg	1 yr	94			92, lymphocytes	181, muscle		(Tulinius et al. 1995)
Asymptomatic	8993T > G	MT-ATP6	Leu156Arg		37			38, lymphocytes	521, muscle		(Tulinius et al. 1995)
Leigh syndrome	8993T > G	MT-ATP6	Leu156Arg					>95, LCLs	35, LCLs^b		(Tatuch and Robinson 1993)
Leigh syndrome	8993T > G	MT-ATP6	Leu156Arg					>95, LCLs	54, LCLs^b		(Tatuch and Robinson 1993)
Leigh syndrome	8993T > G	MT-ATP6	Leu156Arg					>95, LCLs	34, LCLs^b		(Tatuch and Robinson 1993)
MILS	8993T > G	MT-ATP6	Leu156Arg					100, cybrids	39, cybrids		(Carrozzo et al. 2004b)
Leigh syndrome	8993T > G	MT-ATP6	Leu156Arg	<1 yr			95	95, brain 95, kidney 95, liver	117, muscle^b 78, fibroblasts^b		(Tatuch et al. 1992)
Muscle fatigue, headache, memory loss, paresthesias	8993T > G	MT-ATP6	Leu156Arg			19	39	29, urinary epithelium 18, hair 10, platelets	77, platelets		(Carelli et al. 2002)
NARP syndrome	8993T > G	MT-ATP6	Leu156Arg			91	92	91, urinary epithelium 95, hair 87, platelets	4, platelets^b		(Carelli et al. 2002)
NARP/Leigh syndrome	8993T > G	MT-ATP6	Leu156Arg			85	86	88, urinary epithelium 78, hair 80, platelets	9, platelets^b		(Carelli et al. 2002)
Retinitis pigmentosa, ataxia	8993T > G	MT-ATP6	Leu156Arg			55		34, platelets	30, platelets^b		(Carelli et al. 2002)
NARP syndrome	8993T > G	MT-ATP6	Leu156Arg			85		90, platelets	4, platelets^b		(Carelli et al. 2002)
NARP/Leigh syndrome	8993T > G	MT-ATP6	Leu156Arg		88	86		93, urinary epithelium 90, platelets	7, platelets		(Carelli et al. 2002)
Leigh syndrome	8993T > G	MT-ATP6	Leu156Arg				91		75, cybrids	Similar total levels of F₁ as control cells but ↑ complex intermediates	(García et al. 2000)
Leigh syndrome	8993T > G	MT-ATP6	Leu156Arg				100		40, cybrids	Similar total levels of F₁ as control cells but ↑ complex intermediates	(García et al. 2000)
Leigh syndrome	8993T > G	MT-ATP6	Leu156Arg				96		79, cybrids		(Bakare et al. 2021)
Developmental delay, abnormal gait	8993T > G	MT-ATP6	Leu156Arg				91		38, cybrids		(Bakare et al. 2021)
NARP/Leigh syndrome	8993T > G	MT-ATP6	Leu156Arg	<1 yr	>95	>95	>95		42, muscle 33, fibroblasts 24, heart 28, brain		(Uziel et al. 1997)
NARP/Leigh syndrome	8993T > G	MT-ATP6	Leu156Arg		>95				78, muscle 63, fibroblasts		(Uziel et al. 1997)
NARP/Leigh syndrome	8993T > G	MT-ATP6	Leu156Arg		85	>95	73		44, muscle 65, fibroblasts		(Uziel et al. 1997)
NARP/Leigh syndrome	8993T > G	MT-ATP6	Leu156Arg			66	81		59, fibroblasts		(Uziel et al. 1997)
NARP/Leigh syndrome	8993T > G	MT-ATP6	Leu156Arg	9 yr	83	83	83		71, muscle 51, fibroblasts		(Uziel et al. 1997)
NARP/Leigh syndrome	8993T > G	MT-ATP6	Leu156Arg	12 yr	87				58, muscle		(Uziel et al. 1997)
Mitochondrial encephalomyopathy	8993T > G	MT-ATP6	Leu156Arg		>95	>95			27, muscle	↓	(Morava et al. 2006)
Mitochondrial encephalomyopathy	8993T > G	MT-ATP6	Leu156Arg		>95	>95			63, muscle	↓	(Morava et al. 2006)
Mitochondrial encephalomyopathy	8993T > G	MT-ATP6	Leu156Arg		>95	>95			50, muscle	↓	(Morava et al. 2006)
Mitochondrial encephalomyopathy	8993T > G	MT-ATP6	Leu156Arg		>95	>95			54, muscle	↓	(Morava et al. 2006)
Mitochondrial encephalomyopathy	8993T > G	MT-ATP6	Leu156Arg		>95	>95			40, muscle	↓	(Morava et al. 2006)
Mitochondrial encephalomyopathy	8993T > G	MT-ATP6	Leu156Arg		>95	>95			42, muscle	↓	(Morava et al. 2006)
NARP syndrome	m.9127-9128 del AT	MT-ATP6	Frameshift	18 yr	82	15	50		40, fibroblasts		(Mordel et al. 2017)
Leigh syndrome	9176T > C	MT-ATP6	Leu217Pro	<1 yr	>95		>95		100, fibroblasts		(Dionisi-Vici et al. 1998)
Late onset spastic paraplegia-like disorder	9176T > C	MT-ATP6	Leu217Pro		100	100	100	100, urinary sediment	126, fibroblasts	↓ Fully assembled complex V	(Verny et al. 2011)
Late onset spastic paraplegia-like disorder	9176T > C	MT-ATP6	Leu217Pro		100	100	100	100, urinary sediment	74, fibroblasts	↓ Fully assembled complex V	(Verny et al. 2011)
Late onset spastic paraplegia-like disorder	9176T > C	MT-ATP6	Leu217Pro		100	100	100	100, urinary sediment	95, fibroblasts	↓ Fully assembled complex V	(Verny et al. 2011)
Late onset spastic paraplegia-like disorder	9176T > C	MT-ATP6	Leu217Pro		100	100	100	100, urinary sediment	121, fibroblasts	↓ Fully assembled complex V	(Verny et al. 2011)
Late onset spastic paraplegia-like disorder	9176T > C	MT-ATP6	Leu217Pro		100	100	100	100, urinary sediment	97, fibroblasts	↓ Fully assembled complex V	(Verny et al. 2011)
MILS	9176T > G	MT-ATP6	Leu217Arg					100, cybrids	40, cybrids		(Carrozzo et al. 2004b)
Leigh syndrome	9176T > G	MT-ATP6	Leu217Arg				100		20, Fibroblasts		(Carrozzo et al. 2004a)
Myopathy	9185T > C	MT-ATP6	Leu220Pro				98		108, Fibroblasts		(Bakare et al. 2021)

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

[ii] ^bNormalized to protein.

[iii] (AA) Amino acid; (VAF) variant allele frequency; (ATP) ATP synthase; (MILS) maternally inherited Leigh syndrome; (NARP) neuropathy, ataxia, and retinitis pigmentosa; and (LCLs) lymphoblastoid cell lines.