14849 (T > C)

General info

Chr
chrM
Start
14849
End
14849
Ref
T
Alt
C
Mitimpact ID
MI.8544
Gene symbol
MT-CYB
RC complex
III
Ensembl gene ID
Ensembl protein ID
Ensembl transcript ID
Uniprot name
Uniprot ID
Ncbi gene ID
Ncbi protein ID
Gene position
103
AA pos
35
AA ref
S
AA alt
P
Codon substitution
Tca/Cca
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Conservation

PhyloP 100v
-11.74 Conservation Score
PhastCons 100v
0 Conservation Score

Pathogenicity predictors

PolyPhen2
Probably damaging Score and details of the predictor
SIFT
Neutral 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
Neutral Score and details of the predictor
EFIN HD
Damaging Score and details of the predictor
VEST
Pathogenic 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
Medium 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
Uncertain significance
ClinVar July2022 CLNDN
Leigh syndrome;

mitochondrial disease;

exercise intolerance, cardiomyopathy, and septooptic dysplasia
ClinVar July2022 Variation ID
ClinVar July2022 CLNDISDB
Mondo:mondo:0009723, medgen:c0023264, omim:256000, orphanet:orpha506, snomed ct:29570005;

mondo:mondo:0044970, medgen:c0751651, orphanet:orpha68380;

medgen:c4016599
MITOMAP Allele
MITOMAP Disease Het/Hom
-/+
MITOMAP Disease Clinical info
Exit / septo-optic dysplasia
MITOMAP Disease Status
Cfrm
MITOMAP Disease GenBank Freq
0.000%
MITOMAP Disease GenBank Seqs
0 (0)
MITOMAP Disease GenBank Curated refs
3
MITOMAP General GenBank Freq
.
MITOMAP General GenBank Seqs
.
MITOMAP General GenBank Curated refs
.
Gnomad31 filter
Npg
Gnomad31 AC hom
0
Gnomad31 AC het
0
Gnomad31 AF hom
0
Gnomad31 AF het
0
Gnomad31 AN
56431
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
.

14849 (T > G)

General info

Chr
chrM
Start
14849
End
14849
Ref
T
Alt
G
Mitimpact ID
MI.8542
Gene symbol
MT-CYB
RC complex
III
Ensembl gene ID
Ensembl protein ID
Ensembl transcript ID
Uniprot name
Uniprot ID
Ncbi gene ID
Ncbi protein ID
Gene position
103
AA pos
35
AA ref
S
AA alt
A
Codon substitution
Tca/Gca
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Powered by MitoWheel

Conservation

PhyloP 100v
-11.74 Conservation Score
PhastCons 100v
0 Conservation Score

Pathogenicity predictors

PolyPhen2
Probably damaging Score and details of the predictor
SIFT
Neutral Score and details of the predictor
FatHmm
Neutral Score and details of the predictor
FatHMMW
Neutral Score and details of the predictor
PROVEAN
Neutral Score and details of the predictor
Mutation Assessor
High impact Score and details of the predictor
EFIN SP
Neutral 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
Polymorphism Score and details of the predictor
CADD
Neutral Score and details of the predictor
SNAP
Disease Score and details of the predictor
MitoClass 1
Damaging Score and details of the predictor
SNPDryad
Neutral Score and details of the predictor

Pathogenicity meta-predictors

APOGEE
Neutral Score and details of the meta-predictor
CAROL
Neutral 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
Medium 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
.

14849 (T > A)

General info

Chr
chrM
Start
14849
End
14849
Ref
T
Alt
A
Mitimpact ID
MI.8543
Gene symbol
MT-CYB
RC complex
III
Ensembl gene ID
Ensembl protein ID
Ensembl transcript ID
Uniprot name
Uniprot ID
Ncbi gene ID
Ncbi protein ID
Gene position
103
AA pos
35
AA ref
S
AA alt
T
Codon substitution
Tca/Aca
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
-11.74 Conservation Score
PhastCons 100v
0 Conservation Score

Pathogenicity predictors

PolyPhen2
Possibly damaging Score and details of the predictor
SIFT
Neutral Score and details of the predictor
FatHmm
Neutral Score and details of the predictor
FatHMMW
Neutral Score and details of the predictor
PROVEAN
Neutral Score and details of the predictor
Mutation Assessor
High impact Score and details of the predictor
EFIN SP
Neutral 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
Polymorphism Score and details of the predictor
CADD
Neutral Score and details of the predictor
SNAP
Disease Score and details of the predictor
MitoClass 1
Damaging Score and details of the predictor
SNPDryad
Neutral Score and details of the predictor

Pathogenicity meta-predictors

APOGEE
Pathogenic Score and details of the meta-predictor
CAROL
Neutral 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
Medium 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
.
~ 14849 (T/C) 14849 (T/G) 14849 (T/A)
~ 14849 (Tca/Cca) 14849 (Tca/Gca) 14849 (Tca/Aca)
Chr chrM chrM chrM
Start 14849 14849 14849
End 14849 14849 14849
Ref T T T
Alt C G A
MitImpact id MI.8544 MI.8542 MI.8543
Gene symbol MT-CYB MT-CYB MT-CYB
Respiratory Chain complex III III III
Ensembl gene id ENSG00000198727 ENSG00000198727 ENSG00000198727
Ensembl protein id ENSP00000354554 ENSP00000354554 ENSP00000354554
Ensembl transcript id ENST00000361789 ENST00000361789 ENST00000361789
Uniprot name CYB_HUMAN CYB_HUMAN CYB_HUMAN
Uniprot id P00156 P00156 P00156
Ncbi gene id 4519 4519 4519
Ncbi protein id YP_003024038.1 YP_003024038.1 YP_003024038.1
Gene position 103 103 103
AA position 35 35 35
AA ref S S S
AA alt P A T
Codon substitution Tca/Cca Tca/Gca Tca/Aca
PhyloP 100V -11.74 -11.74 -11.74
PhastCons 100V 0 0 0
PolyPhen2 probably_damaging probably_damaging possibly_damaging
PolyPhen2 score 0.98 0.92 0.86
SIFT neutral neutral neutral
SIFT score 0.2 0.5 0.39
FatHmm deleterious neutral neutral
FatHmm score -3.55 -0.63 -1.57
FatHmmW neutral neutral neutral
FatHmmW score 4.41 4.53 4.46
PROVEAN deleterious neutral neutral
PROVEAN score -3.71 -2.22 -2.23
MutationAssessor high impact high impact high impact
MutationAssessor score 4.75 4 5.09
EFIN SP neutral neutral neutral
EFIN SP score 0.93 0.88 0.86
EFIN HD damaging damaging damaging
EFIN HD score 0.05 0.14 0.1
CADD deleterious neutral neutral
CADD score 2.03 1.67 1.72
CADD phred 16.41 14.25 14.55
VEST pvalue 0.05 0.17 0.21
VEST FDR 0.35 0.45 0.45
PANTHER disease disease disease
PANTHER score 0.77 0.55 0.65
PhD-SNP disease disease disease
PhD-SNP score 0.92 0.78 0.82
SNAP disease disease disease
SNAP score 0.75 0.59 0.65
Meta-SNP disease disease disease
Meta-SNP score 0.76 0.67 0.68
Meta-SNP RI 5 3 4
CAROL deleterious neutral neutral
CAROL score 0.99 0.91 0.87
Condel neutral neutral neutral
Condel score 0.11 0.29 0.27
COVEC WMV deleterious deleterious deleterious
COVEC WMV score 2 2 1
MtoolBox deleterious deleterious deleterious
MtoolBox DS 0.85 0.67 0.74
PolyPhen2 transf low impact low impact low impact
PolyPhen2 transf score -2.31 -1.72 -1.47
SIFT_transf medium impact medium impact medium impact
SIFT transf score -0.1 0.22 0.12
MutationAssessor transf high impact high impact high impact
MutationAssessor transf score 3.12 2.44 3.43
CHASM pvalue 0.34 0.57 0.68
CHASM FDR 0.8 0.8 0.85
APOGEE Pathogenic Neutral Pathogenic
APOGEE score 0.74 0.27 0.62
SNPDryad score 1 0.46 0.7
MutationTaster disease_causing_automatic polymorphism polymorphism
MutationTaster score 0 1 1
DEOGEN2 score 0.12 0.02 0.11
Mitoclass.1 damaging damaging damaging
dbSNP 155 id rs207460004 . .
ClinVar October2021 Variation id 9685 . .
ClinVar October2021 CLNSIG Uncertain_significance . .
ClinVar October2021 CLNDN Leigh_syndrome|Mitochondrial_disease|Exercise_intolerance,_cardiomyopathy,_and_septooptic_dysplasia . .
ClinVar October2021 CLNDISDB MONDO:MONDO:0009723,MedGen:C0023264,OMIM:256000,Orphanet:ORPHA506,SNOMED_CT:29570005|MONDO:MONDO:0044970,MedGen:C0751651,Orphanet:ORPHA68380|MedGen:C4016599 . .
COSMIC 90 . . .
MITOMAP Allele T14849C . .
MITOMAP Disease Het/Hom -/+ . .
MITOMAP Disease Clinical info EXIT / Septo-Optic Dysplasia . .
MITOMAP Disease Status Cfrm . .
MITOMAP Disease GenBank Freq 0.000% . .
MITOMAP Disease GenBank Seqs 0 (0) . .
MITOMAP Disease GenBank Curated refs 3 . .
MITOMAP General GenBank Freq . . .
MITOMAP General GenBank Seqs . . .
MITOMAP General Curated refs . . .
gnomAD 3.1 filter npg . .
gnomAD 3.1 AC Homo 0 . .
gnomAD 3.1 AC Het 0 . .
gnomAD 3.1 AF Hom 0 . .
gnomAD 3.1 AF Het 0 . .
gnomAD 3.1 AN 56431 . .
HelixMTdb AC Hom . . .
HelixMTdb AF Hom . . .
HelixMTdb AC Het . . .
HelixMTdb AF Het . . .
HelixMTdb mean ARF . . .
HelixMTdb max ARF . . .
EVmutation MT-CYB_35S|38G:0.102964;205S:0.096786;197L:0.080213;39A:0.077649;36L:0.071004;198L:0.064059 MT-CYB_35S|38G:0.102964;205S:0.096786;197L:0.080213;39A:0.077649;36L:0.071004;198L:0.064059 MT-CYB_35S|38G:0.102964;205S:0.096786;197L:0.080213;39A:0.077649;36L:0.071004;198L:0.064059
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