MitImpact is a collection of pre-computed pathogenicity predictions for all possible nucleotide changes that cause non-synonymous substitution in human mitochondrial protein coding genes. The new version 2.5 greatly updates the tool published in (PMID: 25516408) with the features and contents below.
# | Gene Symbol | Ensembl Gene ID | Ensembl Protein ID | Uniprot Name | Uniprot ID | Ncbi Gene ID | Ncbi Protein ID |
---|---|---|---|---|---|---|---|
1 | MT-ND1 | ENSG00000198888 | ENSP00000354687 | NU1M_HUMAN | P03886 | 4535 | YP_003024026.1 |
2 | MT-ND2 | ENSG00000198763 | ENSP00000355046 | NU2M_HUMAN | P03891 | 4536 | YP_003024027.1 |
3 | MT-ND3 | ENSG00000198840 | ENSP00000355206 | NU3M_HUMAN | P03897 | 4537 | YP_003024033.1 |
4 | MT-ND4 | ENSG00000198886 | ENSP00000354961 | NU4M_HUMAN | P03905 | 4538 | YP_003024031.1 |
5 | MT-ND4L | ENSG00000212907 | ENSP00000354728 | NU4LM_HUMAN | P03901 | 4539 | YP_003024034.1 |
6 | MT-ND5 | ENSG00000198786 | ENSP00000354813 | NU5M_HUMAN | P03915 | 4540 | YP_003024036.1 |
7 | MT-ND6 | ENSG00000198695 | ENSP00000354665 | NU6M_HUMAN | P03923 | 4541 | YP_003024037.1 |
8 | MT-ATP6 | ENSG00000198899 | ENSP00000354632 | ATP6_HUMAN | P00846 | 4508 | YP_003024031.1 |
9 | MT-ATP8 | ENSG00000228253 | ENSP00000355265 | ATP8_HUMAN | P03928 | 4509 | YP_003024030.1 |
10 | MT-CO1 | ENSG00000198804 | ENSP00000354499 | COX1_HUMAN | P00395 | 4512 | YP_003024028.1 |
11 | MT-CO2 | ENSG00000198712 | ENSP00000354876 | COX2_HUMAN | P00403 | 4513 | YP_003024029.1 |
12 | MT-CO3 | ENSG00000198938 | ENSP00000354982 | COX3_HUMAN | P00414 | 4514 | YP_003024032.1 |
13 | MT-CYB | ENSG00000198727 | ENSP00000354554 | CYB_HUMAN | P00156 | 4519 | YP_003024038.1 |
The putative effect of missense mutations within the 13 mitochondrially-encoded proteins was calculated by the following missense pathogenicity predictors:
Mutations were also annotated by these meta-predictors:
Predictions can be obtained from the following web URLs:
Considered known pathogenic mutations:
Position | ref/alt nt Gene | Gene | AA position | Ref/Alt aa | dbSNP id | dbSNP status | MITOMAP phenotype | MITOMAP status |
---|---|---|---|---|---|---|---|---|
Position | ref/alt nt Gene | Gene | AA position | Ref/Alt aa | dbSNP id | dbSNP status | MITOMAP phenotype | MITOMAP status |
15572 | T/C | MT-CYB | 276 | F/L | rs207459996 | Pathogenic | . | . |
15579 | A/G | MT-CYB | 278 | Y/C | rs207460002 | Pathogenic | Multisystem Disorder, EXIT | Confirmed |
15615 | G/A | MT-CYB | 290 | G/D | rs207459997 | Pathogenic | EXIT/Antimycin resistance | Reported |
15620 | C/A | MT-CYB | 292 | L/I | . | . | Leigh Syndrome helper mut | Reported |
15635 | T/C | MT-CYB | 297 | S/P | . | . | Polyvisceral failure | Reported |
15670 | T/A | MT-CYB | 308 | H/Q | rs193302997 | Likely pathogenic | . | . |
15670 | T/G | MT-CYB | 308 | H/Q | rs193302997 | Likely pathogenic | . | . |
15674 | T/C | MT-CYB | 310 | S/P | . | . | LHON | Reported |
15699 | G/C | MT-CYB | 318 | R/P | . | . | Muscle Weakness SNHL and Migraine | Reported |
9016 | A/G | MT-ATP6 | 164 | I/V | . | . | LHON | Reported |
15758 | A/G | MT-CYB | 338 | I/V | rs527236193 | Likely pathogenic | . | . |
15762 | G/A | MT-CYB | 339 | G/E | . | . | MM | Reported |
3308 | T/A | MT-ND1 | 1 | M/K | rs28358582 | Pathogenic|Likely benign | . | . |
3310 | C/T | MT-ND1 | 2 | P/S | . | . | Diabetes/HCM | Reported |
3340 | C/T | MT-ND1 | 12 | P/S | . | . | Encephaloneuromyopathy | Reported |
9035 | T/C | MT-ATP6 | 170 | L/P | . | . | Ataxia syndrome | Reported |
3376 | G/A | MT-ND1 | 24 | E/K | rs397515612 | Pathogenic | LHON MELAS overlap | Cfrm |
3380 | G/A | MT-ND1 | 25 | R/Q | . | . | MELAS | Reported |
3388 | C/A | MT-ND1 | 28 | L/M | rs387906730 | Pathogenic | Materally Inherited Nonsyndromic Deafness | Reported |
3395 | A/G | MT-ND1 | 30 | Y/C | . | . | HCM with hearing loss | Reported |
3397 | A/G | MT-ND1 | 31 | M/V | rs199476120 | Pathogenic | ADPD/PossiblyLVNC-cardiomyopathy associated | Reported |
3418 | A/G | MT-ND1 | 38 | N/D | . | . | AMegL | Reported |
3421 | G/A | MT-ND1 | 39 | V/I | . | . | MIDD | Reported |
3460 | G/A | MT-ND1 | 52 | A/T | rs199476118 | Pathogenic | LHON | Cfrm |
3472 | T/C | MT-ND1 | 56 | F/L | . | . | LHON | Reported |
3481 | G/A | MT-ND1 | 59 | E/K | rs587776433 | Pathogenic | Progressive Encephalomyopathy | Reported |
3488 | T/C | MT-ND1 | 61 | L/P | . | . | LHON (putative) | Reported |
3551 | C/T | MT-ND1 | 82 | A/V | . | . | LHON (putative) | Reported |
9058 | A/G | MT-ATP6 | 178 | T/A | . | . | Possibly LVNC cardiomyopathy-associated | Reported |
3632 | C/T | MT-ND1 | 109 | S/F | . | . | LHON (putative) | Reported |
3635 | G/A | MT-ND1 | 110 | S/N | rs397515507 | Pathogenic | LHON | Cfrm |
3688 | G/A | MT-ND1 | 128 | A/T | . | . | Leigh Syndrome | Reported |
3697 | G/A | MT-ND1 | 131 | G/S | rs199476122 | Pathogenic | MELAS/LS/LDYT | Cfrm |
3700 | G/A | MT-ND1 | 132 | A/T | rs397515508 | Pathogenic | LHON | Cfrm |
9071 | C/T | MT-ATP6 | 182 | S/L | . | . | Potentially functional variant cosegregating with LHON 3635A | Reported |
3713 | T/C | MT-ND1 | 136 | V/A | . | . | LHON (putative) | Reported |
3733 | G/C | MT-ND1 | 143 | E/Q | . | . | LHON | Reported |
3733 | G/A | MT-ND1 | 143 | E/K | rs199476125 | Pathogenic | LHON | Cfrm |
3745 | G/A | MT-ND1 | 147 | A/T | . | . | Possible adaptive high altitude variant | Reported |
3769 | C/G | MT-ND1 | 155 | L/V | . | . | LHON (putative) | Reported |
3781 | T/C | MT-ND1 | 159 | S/P | . | . | LHON (putative) | Reported |
3833 | T/A | MT-ND1 | 176 | L/Q | . | . | PEG | Reported |
3890 | G/A | MT-ND1 | 195 | R/Q | rs587776434 | Pathogenic | Progressive encephalomyopathy/LS/optic atrophy | Cfrm |
3919 | T/C | MT-ND1 | 205 | S/P | . | . | LHON (putative) | Reported |
3928 | G/C | MT-ND1 | 208 | V/L | rs587776442 | Pathogenic | . | . |
3946 | G/A | MT-ND1 | 214 | E/K | rs199476123 | Pathogenic | MELAS | Reported |
3949 | T/C | MT-ND1 | 215 | Y/H | rs199476124 | Pathogenic | MELAS | Reported |
3958 | G/A | MT-ND1 | 218 | G/S | . | . | LHON (putative) | Reported |
3959 | G/A | MT-ND1 | 218 | G/D | . | . | MELAS | Reported |
3995 | A/G | MT-ND1 | 230 | N/S | . | . | MELAS | Reported |
9101 | T/C | MT-ATP6 | 192 | I/T | rs199476134 | Pathogenic | LHON | Reported |
4025 | C/A | MT-ND1 | 240 | T/K | rs397515509 | Pathogenic | . | . |
4025 | C/T | MT-ND1 | 240 | T/M | rs397515509 | Pathogenic | . | . |
4081 | T/C | MT-ND1 | 259 | F/L | . | . | LHON (putative) | Reported |
4123 | A/T | MT-ND1 | 273 | I/F | . | . | LHON (putative) | Reported |
4142 | G/A | MT-ND1 | 279 | R/Q | . | . | Developmental delay,seizure,hypotonia | Reported |
4160 | T/C | MT-ND1 | 285 | L/P | rs199476119 | Pathogenic | LHON | Reported |
4163 | T/C | MT-ND1 | 286 | M/T | . | . | LHON (putative) | Reported |
4171 | C/A | MT-ND1 | 289 | L/M | rs28616230 | Pathogenic | LHON | Cfrm |
4633 | C/G | MT-ND2 | 55 | A/G | . | . | LHON candidate | Reported |
4640 | C/A | MT-ND2 | 57 | I/M | rs387906426 | Pathogenic | LHON | Reported |
4648 | T/C | MT-ND2 | 60 | F/S | . | . | PEG | Reported |
4659 | G/A | MT-ND2 | 64 | A/T | . | . | Possible PD risk factor | Reported |
4681 | T/C | MT-ND2 | 71 | L/P | rs267606889 | Pathogenic | Leigh Syndrome | Reported |
4833 | A/G | MT-ND2 | 122 | T/A | . | . | Diabetes helper mutation,AD,PD | Reported,haplogroup G marker |
4852 | T/A | MT-ND2 | 128 | L/Q | . | . | LHON | Reported |
9166 | T/C | MT-ATP6 | 214 | F/L | rs1057516063 | Likely pathogenic | . | . |
9176 | T/C | MT-ATP6 | 217 | L/P | rs199476135 | Pathogenic | FBSN/Leigh Disease | Cfrm |
9176 | T/G | MT-ATP6 | 217 | L/R | rs199476135 | Pathogenic | Leigh Disease/Spastic Paraplegia | Cfrm |
9185 | T/C | MT-ATP6 | 220 | L/P | rs199476138 | Pathogenic | Leigh Disease/Ataxia syndromes/NARP-like disease | Cfrm |
9191 | T/C | MT-ATP6 | 222 | L/P | rs386829069 | Pathogenic | Leigh Disease | Reported |
5244 | G/A | MT-ND2 | 259 | G/S | rs199476115 | Pathogenic | LHON | Reported |
8381 | A/G | MT-ATP8 | 6 | T/A | . | . | MIDD/LVNC cardiomyopathy-assoc. | Reported |
5452 | C/T | MT-ND2 | 328 | T/M | . | . | Progressive Encephalomyopathy | Reported |
5460 | G/T | MT-ND2 | 331 | A/S | . | . | AD | Reported |
10134 | C/A | MT-ND3 | 26 | Q/K | rs587780529 | Pathogenic | . | . |
10158 | T/C | MT-ND3 | 34 | S/P | rs199476117 | Pathogenic | Leigh Disease | Cfrm |
10191 | T/C | MT-ND3 | 45 | S/P | rs267606890 | Pathogenic | Leigh Disease/Leigh-like Disease/ESOC | Cfrm |
8403 | T/C | MT-ATP8 | 13 | I/T | . | . | Episodic weakness and progressive neuropathy | Reported |
10197 | G/A | MT-ND3 | 47 | A/T | rs267606891 | Pathogenic | Leigh Disease/Dystonia/Stroke/LDYT | Cfrm |
10237 | T/C | MT-ND3 | 60 | I/T | rs193302927 | Pathogenic | LHON | Reported |
10254 | G/A | MT-ND3 | 66 | D/N | rs587776438 | Pathogenic | Leigh Disease | Reported |
8411 | A/G | MT-ATP8 | 16 | M/V | . | . | Severe mitochondrial disorder | Reported |
8418 | T/C | MT-ATP8 | 18 | L/P | rs1057516062 | Likely pathogenic | . | . |
10543 | A/G | MT-ND4L | 25 | H/R | . | . | LHON | Reported |
10563 | T/C | MT-ND4L | 32 | C/R | rs267606892 | Pathogenic | . | . |
10591 | T/G | MT-ND4L | 41 | F/C | . | . | LHON | Reported |
10663 | T/C | MT-ND4L | 65 | V/A | rs193302933 | Pathogenic | LHON | Cfrm |
8481 | C/T | MT-ATP8 | 39 | P/L | . | . | Tetralogy of Fallot patient | Reported |
11232 | T/C | MT-ND4 | 158 | L/P | . | . | CPEO | Reported |
11240 | C/T | MT-ND4 | 161 | L/F | . | . | Leigh Syndrome | Reported |
11253 | T/C | MT-ND4 | 165 | I/T | rs200145866 | Pathogenic | LHON, PD | Reported |
11375 | A/C | MT-ND4 | 206 | K/Q | . | . | found in 1 sCJD patient | Reported |
8528 | T/C | MT-ATP8 | 55 | W/R | rs387906422 | Pathogenic | Infantile cardiomyopathy | Confirmed |
11777 | C/G | MT-ND4 | 340 | R/G | rs28384199 | Pathogenic | . | . |
11777 | C/A | MT-ND4 | 340 | R/S | rs28384199 | Pathogenic | Leigh Disease | Cfrm |
11778 | G/A | MT-ND4 | 340 | R/H | rs199476112 | Pathogenic | LHON/Progressive Dystonia | Cfrm |
8558 | C/T | MT-ATP8 | 65 | P/S | . | . | Possibly LVNC cardiomyopathy-associated | Reported |
8561 | C/G | MT-ATP8 | 66 | P/A | . | . | Ataxia neuropathy,DM,SNHL and hypogonadism | Reported |
11874 | C/A | MT-ND4 | 372 | T/N | . | . | LHON | Reported |
11919 | C/T | MT-ND4 | 387 | S/F | . | . | Thyroid Cancer Cell Line | Reported |
11984 | T/C | MT-ND4 | 409 | Y/H | rs200911567 | Pathogenic | . | . |
12027 | T/C | MT-ND4 | 423 | I/T | . | . | SZ-associated | Reported |
5935 | A/G | MT-CO1 | 11 | N/S | . | . | Prostate Cancer | Reported |
12631 | T/A | MT-ND5 | 99 | S/T | . | . | found in 2 sCJD patients | Reported |
12634 | A/G | MT-ND5 | 100 | I/V | . | . | Thyroid Cancer Cell Line | Reported |
12706 | T/C | MT-ND5 | 124 | F/L | rs267606893 | Pathogenic | Leigh Disease | Cfrm |
12770 | A/G | MT-ND5 | 145 | E/G | rs267606894 | Pathogenic | MELAS | Reported |
12782 | T/G | MT-ND5 | 149 | I/S | . | . | LHON | Reported |
12811 | T/C | MT-ND5 | 159 | Y/H | rs199974018 | Pathogenic | Possible LHON factor | Reported |
5973 | G/A | MT-CO1 | 24 | A/T | . | . | Prostate Cancer | Reported |
12848 | C/T | MT-ND5 | 171 | A/V | rs267606899 | Pathogenic | LHON | Reported |
13042 | G/A | MT-ND5 | 236 | A/T | rs267606898 | Pathogenic | Optic neuropathy/retinopathy/LD | Reported |
13045 | A/C | MT-ND5 | 237 | M/L | rs267606895 | Pathogenic | MELAS/LHON/Leigh overlap syndrome | Reported |
13051 | G/A | MT-ND5 | 239 | G/S | . | . | LHON | Cfrm |
13063 | G/A | MT-ND5 | 243 | V/I | . | . | Adult-onset Encephalopathy/Ataxia | Reported |
13084 | A/T | MT-ND5 | 250 | S/C | rs267606896 | Pathogenic | MELAS/Leigh Disease | Reported |
13094 | T/C | MT-ND5 | 253 | V/A | . | . | Ataxia+PEO/MELAS,LD,myoclonus,fatigue | Reported |
13271 | T/C | MT-ND5 | 312 | L/P | . | . | Exercise intolerance(EXIT) | Reported |
13379 | A/C | MT-ND5 | 348 | H/P | . | . | LHON | Reported |
13511 | A/T | MT-ND5 | 392 | K/M | . | . | Leigh-likesyndrome | Reported |
13513 | G/A | MT-ND5 | 393 | D/N | rs267606897 | Pathogenic | Leigh Disease/MELAS/LHON-MELAS Overlap Syndrome | Cfrm |
13514 | A/G | MT-ND5 | 393 | D/G | rs587776440 | Pathogenic | LeighDisease/MELAS | Cfrm |
13580 | C/G | MT-ND5 | 415 | A/G | . | . | Thyroid Cancer | Reported |
13637 | A/G | MT-ND5 | 434 | Q/R | rs200855215 | Pathogenic | Possible LHON factor | Reported |
13730 | G/A | MT-ND5 | 465 | G/E | rs387906425 | Pathogenic | LHON | Reported |
13831 | C/A | MT-ND5 | 499 | L/M | . | . | Thyroid Cancer Cell Line | Reported |
6081 | G/A | MT-CO1 | 60 | A/T | . | . | Prostate Cancer | Reported |
13967 | C/T | MT-ND5 | 544 | T/M | . | . | Possible LHON factor | Reported |
14063 | T/C | MT-ND5 | 576 | I/T | . | . | Potentially functional variant cosegregating with LHON 3635A | Reported |
14091 | A/T | MT-ND5 | 585 | K/N | . | . | Developmental delay,seizure,hearing loss,diabetes | Reported |
14279 | G/A | MT-ND6 | 132 | S/L | rs869025187 | Pathogenic | LHON | Reported |
14325 | T/C | MT-ND6 | 117 | N/D | rs397515505 | Pathogenic | LHON | Reported |
14340 | C/T | MT-ND6 | 112 | V/M | . | . | SNHL | Reported |
14430 | A/G | MT-ND6 | 82 | W/R | . | . | Thyroid Cancer | Reported |
14439 | G/A | MT-ND6 | 79 | P/S | . | . | Mitochondrial Respiratory Chain Disorder | Reported |
14453 | G/A | MT-ND6 | 74 | A/V | rs199476107 | Pathogenic | MELAS | Reported |
14459 | G/A | MT-ND6 | 72 | A/V | rs199476105 | Pathogenic | LDYT/Leigh Disease | Cfrm |
14482 | C/A | MT-ND6 | 64 | M/I | rs199476108 | Pathogenic | LHON | Cfrm |
14482 | C/G | MT-ND6 | 64 | M/I | rs199476108 | Pathogenic | LHON | Cfrm |
14484 | T/C | MT-ND6 | 64 | M/V | rs199476104 | Pathogenic|Likely pathogenic | LHON | Cfrm |
14487 | T/C | MT-ND6 | 63 | M/V | rs199476109 | Pathogenic | Dystonia/Leigh Disease/Ataxia/Ptosis/Epilepsy | Cfrm |
14495 | A/G | MT-ND6 | 60 | L/S | rs199476106 | Pathogenic | LHON | Cfrm |
14498 | T/C | MT-ND6 | 59 | Y/C | rs869025186 | Pathogenic | LHON | Reported |
14568 | C/T | MT-ND6 | 36 | G/S | rs397515506 | Pathogenic | LHON | Cfrm |
14596 | A/T | MT-ND6 | 26 | I/M | rs387906424 | Pathogenic | LHON | Reported |
14597 | A/G | MT-ND6 | 26 | I/T | rs797045055 | Likely pathogenic | . | . |
14598 | T/C | MT-ND6 | 26 | I/V | rs1057518882 | Likely pathogenic | . | . |
14600 | G/A | MT-ND6 | 25 | P/L | . | . | Leigh Disease/optic atrophy | Reported |
6277 | G/A | MT-CO1 | 125 | G/D | rs281865417 | Pathogenic | . | . |
6328 | C/T | MT-CO1 | 142 | S/F | rs267606883 | Pathogenic | EXIT (Exercise Intolerance) | Reported |
6340 | C/T | MT-CO1 | 146 | T/I | . | . | Prostate Cancer | Reported |
8668 | T/C | MT-ATP6 | 48 | W/R | . | . | LHON | Reported |
6480 | G/A | MT-CO1 | 193 | V/I | rs199476128 | Pathogenic | Prostate Cancer/enriched in POAG cohort | Reported |
6489 | C/G | MT-CO1 | 196 | L/V | rs28461189 | Pathogenic | . | . |
6489 | C/A | MT-CO1 | 196 | L/I | rs28461189 | Pathogenic | Therapy-Resistant Epilepsy | Reported |
6597 | C/A | MT-CO1 | 232 | Q/K | . | . | MELAS-like syndrome | Reported |
6721 | T/C | MT-CO1 | 273 | M/T | rs199476127 | Pathogenic | Acquired Idiopathic Sideroblastic Anemia | Reported |
6742 | T/C | MT-CO1 | 280 | I/T | rs199476126 | Pathogenic | Acquired Idiopathic Sideroblastic Anemia | Reported |
8528 | T/C | MT-ATP6 | 1 | M/T | rs387906422 | Pathogenic | Infantile cardiomyopathy | Confirmed |
6955 | G/A | MT-CO1 | 351 | G/D | . | . | Mild EXIT and MR | Reported |
7023 | G/A | MT-CO1 | 374 | V/M | . | . | MELAS-like syndrome | Reported |
7041 | G/A | MT-CO1 | 380 | V/I | . | . | Prostate Cancer | Reported |
7080 | T/C | MT-CO1 | 393 | F/L | . | . | Prostate Cancer | Reported |
7083 | A/G | MT-CO1 | 394 | I/V | . | . | Prostate Cancer | Reported |
8741 | T/G | MT-ATP6 | 72 | L/R | . | . | MILS protective factor | Reported |
7275 | T/C | MT-CO1 | 458 | S/P | rs267606884 | Pathogenic | . | . |
7305 | A/C | MT-CO1 | 468 | M/L | . | . | Prostate Cancer | Reported |
7587 | T/C | MT-CO2 | 1 | M/T | rs199474825 | Pathogenic | Mitochondrial Encephalomyopathy | Reported |
7623 | C/T | MT-CO2 | 13 | T/I | . | . | LHON | Reported |
7637 | G/A | MT-CO2 | 18 | E/K | . | . | PD risk factor | Reported |
7671 | T/A | MT-CO2 | 29 | M/K | rs199474827 | Pathogenic | MM | Reported |
7706 | G/A | MT-CO2 | 41 | A/T | . | . | Alpers-Huttennlocher-like | Reported |
8795 | A/G | MT-ATP6 | 90 | H/R | . | . | MILS protective factor | Reported |
7877 | A/C | MT-CO2 | 98 | K/Q | . | . | PEG glaucoma | Reported |
7989 | T/C | MT-CO2 | 135 | L/P | . | . | Rhabdomyolysis | Reported |
8009 | G/A | MT-CO2 | 142 | V/M | rs199474826 | Pathogenic | . | . |
8010 | T/C | MT-CO2 | 142 | V/A | . | . | Developmental delay,ataxia,seizure,hypotonia,lactic acidosis | Reported |
8021 | A/G | MT-CO2 | 146 | I/V | . | . | Asthenozoospermia | Reported |
8108 | A/G | MT-CO2 | 175 | I/V | . | . | SNHL | Reported |
8836 | A/G | MT-ATP6 | 104 | M/V | . | . | LHON | Reported |
8839 | G/C | MT-ATP6 | 105 | A/P | rs369202065 | Pathogenic | . | . |
8839 | G/A | MT-ATP6 | 105 | A/T | rs369202065 | Pathogenic | . | . |
9237 | G/A | MT-CO3 | 11 | V/M | rs1057516064 | Likely pathogenic | . | . |
9267 | G/C | MT-CO3 | 21 | A/P | . | . | MIDD | Reported |
8851 | T/C | MT-ATP6 | 109 | W/R | rs199476136 | Pathogenic | BSN | Reported |
9387 | G/A | MT-CO3 | 61 | V/M | . | . | Asthenozoospermia | Reported |
9478 | T/C | MT-CO3 | 91 | V/A | rs587776437 | Pathogenic | Leigh Disease | Reported |
9544 | G/A | MT-CO3 | 113 | G/E | . | . | Sporadic bilateral optic neuropathy | Reported |
8558 | C/T | MT-ATP6 | 11 | A/V | . | . | Possibly LVNC cardiomyopathy-associated | Reported |
9660 | A/C | MT-CO3 | 152 | M/L | . | . | LHON | Reported |
8890 | A/G | MT-ATP6 | 122 | K/E | . | . | Juevnile-onset metabolic syndrome | Reported |
9738 | G/T | MT-CO3 | 178 | A/S | . | . | LHON | Reported |
9789 | T/C | MT-CO3 | 195 | S/P | . | . | Myopathy | Reported |
8561 | C/G | MT-ATP6 | 12 | P/R | . | . | Ataxia neuropathy,DM,SNHL,and hypogonadism | Reported |
9804 | G/A | MT-CO3 | 200 | A/T | rs200613617 | Pathogenic | LHON | Reported |
9957 | T/C | MT-CO3 | 251 | F/L | . | . | PEM/MELAS/NAION | Reported |
9972 | A/C | MT-CO3 | 256 | I/L | . | . | EXIT & APS2 - possible link | Reported |
14753 | C/T | MT-CYB | 3 | P/S | rs527236162 | Likely pathogenic | . | . |
14766 | C/A | MT-CYB | 7 | T/N | rs193302980 | Likely pathogenic | . | . |
14766 | C/T | MT-CYB | 7 | T/I | rs193302980,rs527236041 | Likely pathogenic | . | . |
14766 | C/G | MT-CYB | 7 | T/S | rs193302980 | Likely pathogenic | . | . |
14783 | T/G | MT-CYB | 13 | L/V | rs193302982 | Likely pathogenic | . | . |
14783 | T/A | MT-CYB | 13 | L/M | rs193302982 | Likely pathogenic | . | . |
14784 | T/C | MT-CYB | 13 | L/S | rs527236163 | Likely pathogenic | . | . |
14831 | G/A | MT-CYB | 29 | A/T | rs199795644 | Pathogenic | LHON | Reported |
14841 | A/G | MT-CYB | 32 | N/S | . | . | LHON helper mut. | Reported |
14846 | G/A | MT-CYB | 34 | G/S | rs207459998 | Pathogenic | EXIT | Reported |
14849 | T/C | MT-CYB | 35 | S/P | rs207460004 | Pathogenic | EXIT/Septo-Optic Dysplasia | Confirmed |
14864 | T/C | MT-CYB | 40 | C/R | . | . | MELAS | Confirmed |
14891 | C/G | MT-CYB | 49 | L/V | rs386419981 | Likely pathogenic | . | . |
14905 | G/T | MT-CYB | 53 | M/I | rs193302983 | Likely pathogenic | . | . |
14905 | G/C | MT-CYB | 53 | M/I | rs193302983 | Likely pathogenic | . | . |
14985 | G/A | MT-CYB | 80 | R/H | rs207459995 | Pathogenic | . | . |
15024 | G/A | MT-CYB | 93 | C/Y | . | . | Possible DEAF modifier | Reported |
15060 | G/A | MT-CYB | 105 | G/E | rs1057516072 | Likely pathogenic | . | . |
8950 | G/A | MT-ATP6 | 142 | V/I | . | . | LDYT | Reported |
15092 | G/A | MT-CYB | 116 | G/S | . | . | MELAS | Reported |
15098 | A/G | MT-CYB | 118 | I/V | rs527236172 | Likely pathogenic | . | . |
15197 | T/C | MT-CYB | 151 | S/P | rs207460001 | Pathogenic | EXIT | Reported |
15209 | T/C | MT-CYB | 155 | Y/H | . | . | Prader-Willi syndrome | Reported |
15243 | G/A | MT-CYB | 166 | G/E | . | . | HCM | Reported |
15246 | G/A | MT-CYB | 167 | G/D | rs1057516075 | Likely pathogenic | . | . |
8969 | G/A | MT-ATP6 | 148 | S/N | rs794726857 | Pathogenic | Mitochondrial myopathy,lactic acidosis and sideroblastic anemia(MLASA) | Reported |
15301 | G/T | MT-CYB | 185 | L/F | rs193302991 | Likely pathogenic | . | . |
15301 | G/C | MT-CYB | 185 | L/F | rs193302991 | Likely pathogenic | . | . |
15314 | G/A | MT-CYB | 190 | A/T | rs527236176 | Likely pathogenic | . | . |
15323 | G/A | MT-CYB | 193 | A/T | rs527236177 | Likely pathogenic | . | . |
15326 | A/G | MT-CYB | 194 | T/A | rs2853508 | Likely pathogenic | . | . |
15349 | C/A | MT-CYB | 201 | H/Q | rs527236201 | Likely pathogenic,Likely pathogenic | . | . |
15363 | A/G | MT-CYB | 206 | N/S | rs527236182 | Likely pathogenic | . | . |
15395 | A/G | MT-CYB | 217 | K/E | . | . | Possible LHON factor | Reported |
15431 | G/C | MT-CYB | 229 | A/P | rs193302993 | Likely pathogenic | . | . |
15431 | G/A | MT-CYB | 229 | A/T | rs527236208,rs193302993 | Likely pathogenic | . | . |
15431 | G/T | MT-CYB | 229 | A/S | rs193302993 | Likely pathogenic | . | . |
15452 | C/A | MT-CYB | 236 | L/I | rs193302994,rs527236209 | Likely pathogenic | . | . |
15452 | C/T | MT-CYB | 236 | L/F | rs193302994 | Likely pathogenic | . | . |
15453 | T/C | MT-CYB | 236 | L/P | rs527236184 | Likely pathogenic | Isolated complex III deficiency | Reported |
15458 | T/C | MT-CYB | 238 | S/P | rs527236185 | Likely pathogenic | . | . |
15459 | C/T | MT-CYB | 238 | S/F | rs527236186 | Likely pathogenic | . | . |
8989 | G/C | MT-ATP6 | 155 | A/P | rs587776444 | Pathogenic | . | . |
15498 | G/A | MT-CYB | 251 | G/D | rs207460003 | Pathogenic | HiCM/WPW,DEAF | Reported |
8993 | T/G | MT-ATP6 | 156 | L/R | rs199476133 | Pathogenic | NARP/Leigh Disease/MILS/other | Cfrm |
8993 | T/C | MT-ATP6 | 156 | L/P | rs199476133 | Pathogenic | NARP/Leigh Disease/MILS/other | Cfrm |
Reported means that one or more papers have hypothesized a pathologic role for that mutation;
Reported – haplogroup indicates that the considered mutation characterizes also a specific human mtDNA haplogroup;
Confirmed indicates that the mutation is disease-causing.
APOGEE
APOGEE is a LMT-based consensus classifier. LMT (Logistic Model Tree) is a machine learning technique which consists of a combination of decision trees and logistic regressions at the leaves. The model is evaluated on the basis of some predictor variables that can be used for making decisions in the tree construction and selected for logistic models. The difference between decision tree and LMT is that the former classifies all the instances belonging to a leaf with the class having the highest frequency in the leaf. While LMT constructs a logistic model for classifying the instances in the same leaf by giving, to each instance, the probability of belonging to a class.
APOGEE handles two pathogenicity classes: neutral and pathogenic. Mutations are considered as instances of the following predictors:
Once defined the classification function, we implemented and tested a bootstrap strategy, which randomly selected 70% of the pathogenic mutations and considered the same number of neutral mutations. In brief, for 100 iterations, we run this algorithm:
The LMT models generated during the 100 iterations can be downloaded here.
Method | Accuracy | Precision | FDR | MCC | MCR |
MetaSNP | 0.54 | 0.29 | 0.71 | 0.09 | 45.83 |
CAROL | 0.59 | 0.33 | 0.67 | 0.13 | 40.28 |
Condel | 0.49 | 0.23 | 0.78 | -0.08 | 51.16 |
COVERC WMV | 0.59 | 0.33 | 0.67 | 0.12 | 41.27 |
MToolBox DS | 0.48 | 0.28 | 0.72 | 0.06 | 51.62 |
APOGEE bootstrap | 0.84 | 0.73 | 0.27 | 0.59 | 15.97 |