11778 (G > A)

General info

Chr
chrM
Start
11778
End
11778
Ref
G
Alt
A
Mitimpact ID
MI.18470
Gene symbol
MT-ND4
RC complex
I
Ensembl gene ID
Ensembl protein ID
Ensembl transcript ID
Uniprot name
Uniprot ID
Ncbi gene ID
Ncbi protein ID
Gene position
1019
AA pos
340
AA ref
R
AA alt
H
Codon substitution
cGc/cAc
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Conservation

PhyloP 100v
4.4 Conservation Score
PhastCons 100v
1 Conservation Score

Pathogenicity predictors

PolyPhen2
Probably damaging Score and details of the predictor
SIFT
Deleterious Score and details of the predictor
FatHmm
Deleterious Score and details of the predictor
FatHMMW
Neutral Score and details of the predictor
PROVEAN
Deleterious Score and details of the predictor
Mutation Assessor
High impact Score and details of the predictor
EFIN SP
Damaging Score and details of the predictor
EFIN HD
Damaging Score and details of the predictor
VEST
Neutral Score and details of the predictor
PANTHER
Disease Score and details of the predictor
PhD-SNP
Disease Score and details of the predictor
MutationTaster
Disease causing automatic Score and details of the predictor
CADD
Deleterious Score and details of the predictor
SNAP
Disease Score and details of the predictor
MitoClass 1
Damaging Score and details of the predictor
SNPDryad
Pathogenic Score and details of the predictor

Pathogenicity meta-predictors

APOGEE
Pathogenic Score and details of the meta-predictor
CAROL
Deleterious Score and details of the meta-predictor
Condel
Neutral Score and details of the meta-predictor
COVEC WMV
Deleterious Score and details of the meta-predictor
Meta SNP
Disease Score and details of the meta-predictor
MtoolBox
Deleterious Score and details of the meta-predictor
DEOGEN2
Neutral Score and details of the meta-predictor

Cancer-specific predictors

PolyPhen2 transf
Low impact Score and details of the cancer-specific predictor
SIFT transf
Low impact Score and details of the cancer-specific predictor
MutationAssessor transf
High impact Score and details of the cancer-specific predictor
CHASM
Neutral Score and details of the cancer-specific predictor

Databases of Phenotypes

ClinVar July2022 CLNSIG
.
ClinVar July2022 CLNDN
.
ClinVar July2022 Variation ID
ClinVar July2022 CLNDISDB
.
MITOMAP Allele
MITOMAP Disease Het/Hom
+/+
MITOMAP Disease Clinical info
Lhon / progressive dystonia
MITOMAP Disease Status
Cfrm
MITOMAP Disease GenBank Freq
0.000%
MITOMAP Disease GenBank Seqs
187 (0)
MITOMAP Disease GenBank Curated refs
395
MITOMAP General GenBank Freq
.
MITOMAP General GenBank Seqs
.
MITOMAP General GenBank Curated refs
.
Gnomad31 filter
Pass
Gnomad31 AC hom
11
Gnomad31 AC het
13
Gnomad31 AF hom
0.00019495595
Gnomad31 AF het
0.0002304025
Gnomad31 AN
56423
HelixMTdb AC hom
44
HelixMTdb AF hom
0.00022450926
HelixMTdb AC het
34
HelixMTdb AF het
0.00017348444
HelixMTdb mean ARF
0.37469
HelixMTdb max ARF
0.91005
COSMIC 90
.
dbSNP 155

Residue interaction

EVmutation
Site A-B InterP
Site A-B IntraP
ΔΔG intra
ΔΔG intra interface
ΔΔG inter

Compensated Pathogenic Deviations

Frequency
.
AA ref
.
CPD AA alt
.
Aln pos
.
RefSeq protein ID
.
Species name
.
Ncbi taxon ID
.

11778 (G > T)

General info

Chr
chrM
Start
11778
End
11778
Ref
G
Alt
T
Mitimpact ID
MI.18468
Gene symbol
MT-ND4
RC complex
I
Ensembl gene ID
Ensembl protein ID
Ensembl transcript ID
Uniprot name
Uniprot ID
Ncbi gene ID
Ncbi protein ID
Gene position
1019
AA pos
340
AA ref
R
AA alt
L
Codon substitution
cGc/cTc
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
4.4 Conservation Score
PhastCons 100v
1 Conservation Score

Pathogenicity predictors

PolyPhen2
Probably damaging Score and details of the predictor
SIFT
Deleterious Score and details of the predictor
FatHmm
Deleterious Score and details of the predictor
FatHMMW
Neutral Score and details of the predictor
PROVEAN
Deleterious Score and details of the predictor
Mutation Assessor
High impact Score and details of the predictor
EFIN SP
Damaging Score and details of the predictor
EFIN HD
Damaging Score and details of the predictor
VEST
Neutral Score and details of the predictor
PANTHER
Neutral Score and details of the predictor
PhD-SNP
Disease Score and details of the predictor
MutationTaster
Polymorphism Score and details of the predictor
CADD
Deleterious Score and details of the predictor
SNAP
Disease Score and details of the predictor
MitoClass 1
Damaging Score and details of the predictor
SNPDryad
Pathogenic Score and details of the predictor

Pathogenicity meta-predictors

APOGEE
Pathogenic Score and details of the meta-predictor
CAROL
Deleterious Score and details of the meta-predictor
Condel
Neutral Score and details of the meta-predictor
COVEC WMV
Deleterious Score and details of the meta-predictor
Meta SNP
Disease Score and details of the meta-predictor
MtoolBox
Deleterious Score and details of the meta-predictor
DEOGEN2
Neutral Score and details of the meta-predictor

Cancer-specific predictors

PolyPhen2 transf
Low impact Score and details of the cancer-specific predictor
SIFT transf
Low impact Score and details of the cancer-specific predictor
MutationAssessor transf
High impact Score and details of the cancer-specific predictor
CHASM
Neutral Score and details of the cancer-specific predictor

Databases of Phenotypes

ClinVar July2022 CLNSIG
.
ClinVar July2022 CLNDN
.
ClinVar July2022 Variation ID
ClinVar July2022 CLNDISDB
.
MITOMAP Allele
.
MITOMAP Disease Het/Hom
.
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease GenBank Freq
.
MITOMAP Disease GenBank Seqs
.
MITOMAP Disease GenBank Curated refs
.
MITOMAP General GenBank Freq
.
MITOMAP General GenBank Seqs
.
MITOMAP General GenBank Curated refs
.
Gnomad31 filter
.
Gnomad31 AC hom
.
Gnomad31 AC het
.
Gnomad31 AF hom
.
Gnomad31 AF het
.
Gnomad31 AN
.
HelixMTdb AC hom
.
HelixMTdb AF hom
.
HelixMTdb AC het
.
HelixMTdb AF het
.
HelixMTdb mean ARF
.
HelixMTdb max ARF
.
COSMIC 90
.
dbSNP 155

Residue interaction

EVmutation
Site A-B InterP
Site A-B IntraP
ΔΔG intra
ΔΔG intra interface
ΔΔG inter

Compensated Pathogenic Deviations

Frequency
.
AA ref
.
CPD AA alt
.
Aln pos
.
RefSeq protein ID
.
Species name
.
Ncbi taxon ID
.

11778 (G > C)

General info

Chr
chrM
Start
11778
End
11778
Ref
G
Alt
C
Mitimpact ID
MI.18469
Gene symbol
MT-ND4
RC complex
I
Ensembl gene ID
Ensembl protein ID
Ensembl transcript ID
Uniprot name
Uniprot ID
Ncbi gene ID
Ncbi protein ID
Gene position
1019
AA pos
340
AA ref
R
AA alt
P
Codon substitution
cGc/cCc
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
4.4 Conservation Score
PhastCons 100v
1 Conservation Score

Pathogenicity predictors

PolyPhen2
Probably damaging Score and details of the predictor
SIFT
Deleterious Score and details of the predictor
FatHmm
Deleterious Score and details of the predictor
FatHMMW
Neutral Score and details of the predictor
PROVEAN
Deleterious Score and details of the predictor
Mutation Assessor
High impact Score and details of the predictor
EFIN SP
Damaging Score and details of the predictor
EFIN HD
Damaging Score and details of the predictor
VEST
Pathogenic Score and details of the predictor
PANTHER
Neutral Score and details of the predictor
PhD-SNP
Disease Score and details of the predictor
MutationTaster
Polymorphism Score and details of the predictor
CADD
Deleterious Score and details of the predictor
SNAP
Disease Score and details of the predictor
MitoClass 1
Damaging Score and details of the predictor
SNPDryad
Pathogenic Score and details of the predictor

Pathogenicity meta-predictors

APOGEE
Pathogenic Score and details of the meta-predictor
CAROL
Deleterious Score and details of the meta-predictor
Condel
Neutral Score and details of the meta-predictor
COVEC WMV
Deleterious Score and details of the meta-predictor
Meta SNP
Disease Score and details of the meta-predictor
MtoolBox
Deleterious Score and details of the meta-predictor
DEOGEN2
Neutral Score and details of the meta-predictor

Cancer-specific predictors

PolyPhen2 transf
Low impact Score and details of the cancer-specific predictor
SIFT transf
Low impact Score and details of the cancer-specific predictor
MutationAssessor transf
High impact Score and details of the cancer-specific predictor
CHASM
Neutral Score and details of the cancer-specific predictor

Databases of Phenotypes

ClinVar July2022 CLNSIG
.
ClinVar July2022 CLNDN
.
ClinVar July2022 Variation ID
ClinVar July2022 CLNDISDB
.
MITOMAP Allele
.
MITOMAP Disease Het/Hom
.
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease GenBank Freq
.
MITOMAP Disease GenBank Seqs
.
MITOMAP Disease GenBank Curated refs
.
MITOMAP General GenBank Freq
.
MITOMAP General GenBank Seqs
.
MITOMAP General GenBank Curated refs
.
Gnomad31 filter
.
Gnomad31 AC hom
.
Gnomad31 AC het
.
Gnomad31 AF hom
.
Gnomad31 AF het
.
Gnomad31 AN
.
HelixMTdb AC hom
.
HelixMTdb AF hom
.
HelixMTdb AC het
.
HelixMTdb AF het
.
HelixMTdb mean ARF
.
HelixMTdb max ARF
.
COSMIC 90
.
dbSNP 155

Residue interaction

EVmutation
Site A-B InterP
Site A-B IntraP
ΔΔG intra
ΔΔG intra interface
ΔΔG inter

Compensated Pathogenic Deviations

Frequency
.
AA ref
.
CPD AA alt
.
Aln pos
.
RefSeq protein ID
.
Species name
.
Ncbi taxon ID
.
~ 11778 (G/A) 11778 (G/T) 11778 (G/C)
~ 11778 (cGc/cAc) 11778 (cGc/cTc) 11778 (cGc/cCc)
Chr chrM chrM chrM
Start 11778 11778 11778
End 11778 11778 11778
Ref G G G
Alt A T C
MitImpact id MI.18470 MI.18468 MI.18469
Gene symbol MT-ND4 MT-ND4 MT-ND4
Respiratory Chain complex I I I
Ensembl gene id ENSG00000198886 ENSG00000198886 ENSG00000198886
Ensembl protein id ENSP00000354961 ENSP00000354961 ENSP00000354961
Ensembl transcript id ENST00000361381 ENST00000361381 ENST00000361381
Uniprot name NU4M_HUMAN NU4M_HUMAN NU4M_HUMAN
Uniprot id P03905 P03905 P03905
Ncbi gene id 4538 4538 4538
Ncbi protein id YP_003024035.1 YP_003024035.1 YP_003024035.1
Gene position 1019 1019 1019
AA position 340 340 340
AA ref R R R
AA alt H L P
Codon substitution cGc/cAc cGc/cTc cGc/cCc
PhyloP 100V 4.4 4.4 4.4
PhastCons 100V 1 1 1
PolyPhen2 probably_damaging probably_damaging probably_damaging
PolyPhen2 score 1 1 1
SIFT deleterious deleterious deleterious
SIFT score 0 0 0
FatHmm deleterious deleterious deleterious
FatHmm score -3.75 -3.21 -4.4
FatHmmW neutral neutral neutral
FatHmmW score 4.44 4.45 4.44
PROVEAN deleterious deleterious deleterious
PROVEAN score -4.74 -6.64 -6.64
MutationAssessor high impact high impact high impact
MutationAssessor score 4.61 3.56 4.61
EFIN SP damaging damaging damaging
EFIN SP score 0.18 0.39 0.4
EFIN HD damaging damaging damaging
EFIN HD score 0.13 0.26 0.2
CADD deleterious deleterious deleterious
CADD score 4.56 4.46 4.35
CADD phred 24.4 24.2 24.1
VEST pvalue 0.21 0.06 0.03
VEST FDR 0.45 0.35 0.35
PANTHER disease neutral neutral
PANTHER score 0.63 0.5 0.28
PhD-SNP disease disease disease
PhD-SNP score 0.87 0.92 0.91
SNAP disease disease disease
SNAP score 0.8 0.8 0.87
Meta-SNP disease disease disease
Meta-SNP score 0.72 0.75 0.72
Meta-SNP RI 4 5 4
CAROL deleterious deleterious deleterious
CAROL score 1 1 1
Condel neutral neutral neutral
Condel score 0 0 0
COVEC WMV deleterious deleterious deleterious
COVEC WMV score 6 6 6
MtoolBox deleterious deleterious deleterious
MtoolBox DS 0.85 0.84 0.83
PolyPhen2 transf low impact low impact low impact
PolyPhen2 transf score -3.54 -3.54 -3.54
SIFT_transf low impact low impact low impact
SIFT transf score -1.48 -1.48 -1.48
MutationAssessor transf high impact high impact high impact
MutationAssessor transf score 3.44 2.4 3.44
CHASM pvalue 0.77 0.02 0.13
CHASM FDR 0.85 0.8 0.8
APOGEE Pathogenic Pathogenic Pathogenic
APOGEE score 0.97 0.81 0.76
SNPDryad score 1 1 0.99
MutationTaster disease_causing_automatic polymorphism polymorphism
MutationTaster score 0 1 1
DEOGEN2 score 0.24 0.21 0.4
Mitoclass.1 damaging damaging damaging
dbSNP 155 id rs199476112 . .
ClinVar October2021 Variation id . . .
ClinVar October2021 CLNSIG . . .
ClinVar October2021 CLNDN . . .
ClinVar October2021 CLNDISDB . . .
COSMIC 90 . . .
MITOMAP Allele G11778A . .
MITOMAP Disease Het/Hom +/+ . .
MITOMAP Disease Clinical info LHON / Progressive Dystonia . .
MITOMAP Disease Status Cfrm . .
MITOMAP Disease GenBank Freq 0.000% . .
MITOMAP Disease GenBank Seqs 187 (0) . .
MITOMAP Disease GenBank Curated refs 395 . .
MITOMAP General GenBank Freq . . .
MITOMAP General GenBank Seqs . . .
MITOMAP General Curated refs . . .
gnomAD 3.1 filter PASS . .
gnomAD 3.1 AC Homo 11 . .
gnomAD 3.1 AC Het 13 . .
gnomAD 3.1 AF Hom 0.00019495595 . .
gnomAD 3.1 AF Het 0.0002304025 . .
gnomAD 3.1 AN 56423 . .
HelixMTdb AC Hom 44 . .
HelixMTdb AF Hom 0.00022450926 . .
HelixMTdb AC Het 34 . .
HelixMTdb AF Het 0.00017348444 . .
HelixMTdb mean ARF 0.37469 . .
HelixMTdb max ARF 0.91005 . .
EVmutation MT-ND4_340R|344L:0.142928;341I:0.12325;342M:0.084446;343I:0.079417 MT-ND4_340R|344L:0.142928;341I:0.12325;342M:0.084446;343I:0.079417 MT-ND4_340R|344L:0.142928;341I:0.12325;342M:0.084446;343I:0.079417
Site A InterP . . .
Site B InterP . . .
Covariation Score InterP . . .
Site A IntraP . . .
Site B IntraP . . .
Covariation Score IntraP . . .
CPD AA ref . . .
CPD AA alt . . .
CPD Aln pos . . .
CPD Frequency . . .
CPD Species name . . .
CPD RefSeq Protein ID . . .
CPD Ncbi Taxon id . . .
DDG intra . . .
DDG intra interface . . .
DDG inter . . .
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
For more info, please check the output legend.
Score:  
0
  [min -20, max 10]
  • Predicted accelerated evolution:  score <= 0
  • Conserved:  score > 0
Score:  
0
  [min 0, max 1]
  • Non-conserved:  score <= 0.9
  • Conserved:  score > 0.9 (soft threshold)
Score:  
0
  [min 0, max 1]
  • Neutral:  score <= 0.15
  • Possibly damaging:  0.15 < score <= 0.85
  • Probably damaging:  score > 0.85
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.05
  • Deleterious:  score <= 0.05
Score:  
0
  [min -15, max 10]
  • Neutral:  score > -3
  • Deleterious:  score <= -3
Score:  
0
  [min -3, max 6]
  • Neutral:  score > -1.5
  • Deleterious:  score <= -1.5
Score:  
0
  [min -14, max 14]
  • Neutral:  score > -2.5
  • Deleterious:  score <= -2.5 (soft threshold)
Score:  
0
  [min -6, max 6]
  • Neutral:  score <= 0.8
  • Low impact:  0.8 < score <= 1.9
  • Medium impact:  1.9 < score <= 3.5
  • High impact:  score > 3.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.6
  • Damaging:  score <= 0.6
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.28
  • Damaging:  score <= 0.28
Phred score:  
0
  [min 0, max 35]
  • Neutral:  score < 20 (soft threshold)
  • Deleterious:  score >= 20
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Polymorphism:  score < 0.5
  • Disease causing:  score >= 0.5
P-value:  
0
  [min 0, max 1]
  • Neutral:  p-value > 0.05
  • Pathogenic:  p-value <= 0.05
Score:  
0
  [min 0, max 1]
No hard-thresholds were indicated by authors (ref). Indicatively:
  • Neutral:  score < 0.9
  • Pathogenic:  score >= 0.9
No score. Categorical only
Please refer to Additional File 14: Table S10 for further details.
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.98
  • Deleterious:  score >= 0.98
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Deleterious:  score >= 0.5
Score:  
0
  [min -6, max 6]
  • Neutral:  score < 0
  • Deleterious:  score > 0
  • Inaccurate prediction:  score = 0
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Deleterious:  score >= 0.5
DS score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.43
  • Deleterious:  score >= 0.43
Score:  
0
  [min 0, max 1]
  • Neutral:  score <= 0.5
  • Pathogenic:  score > 0.5
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1 (soft threshold)
  • Medium impact:  -1 < score < 1.5 (soft threshold)
  • High impact:  score >= 1.5 (soft threshold)
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1
  • Medium impact:  -1 < score < 2 (soft threshold)
  • High impact:  score >= 2 (soft threshold)
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1
  • Medium impact:  -1 < score < 2 (soft threshold)
  • High impact:  score >= 2 (soft threshold)
P-value:  
0
  [min 0, max 1]
  • Neutral:  FDR > 0.2
  • Driver:  FDR <= 0.2
The frequency of a CPD variant is proportional to the
number of aligned orthologous sequences that
carry a specific human pathogenic variant as
wild-type amino acid on the total number of aligned
sequences.

For more info, please check the output legend