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Legend of the output


    General info

  1. MitImpact id: variant identifier in MitImpact
  2. Chr: the reference sequence of the human mtDNA is the Revised Cambridge Reference Sequence; NCBI accession number: NC_012920.1
  3. Start: genomic position of the variant
  4. Ref: reference nucleotide
  5. Alt: alternative nucleotide
  6. Gene symbol: official gene symbol
  7. Gene position: variant position relative to the coordinates of the gene or the genomic region (D-loop or intergenic) involved
  8. Gene start: start of the gene or the genomic region (D-loop or intergenic) involved
  9. Gene end: end of the gene or the genomic region (D-loop or intergenic) involved
  10. Gene strand: strand of the gene or the genomic region (D-loop or intergenic) involved
  11. Codon substitution: codon substitution relative to the genomic variant. It only applies to variants in protein-coding genes. Please note that for some protein-coding genes termination codon is completed by the addition of 3' A residues to the mRNA. These cases are indicated with a "."
  12. AA pos: amino acid position
  13. AA ref: reference amino acid. It only applies to variants in protein-coding genes. Termination codons are indicated with a "*". Please note that for some protein-coding genes termination codon is completed by the addition of 3' A residues to the mRNA. These cases are indicated with a "."
  14. AA alt: alternative amino acid. It only applies to variants in protein-coding genes. Termination codons are indicated with a "*". Please note that for some protein-coding genes termination codon is completed by the addition of 3' A residues to the mRNA. These cases are indicated with a "."
  15. General functional effect: effect of the variant on the genomic sequence, assessed through SnpEff. If the variant is localized in a protein-coding sequence, the variant can be: missense, stop lost, stop gained, stop retained variant, start lost, start retained variant or synonymous variant. Otherwise, it can be a non-coding or intergenic variant. ()
  16. Detailed functional effect: (in a popup) detailed effect of the variant on the genomic sequence, assessed through SnpEff. For the complete description of each potential functional effect, please visit the SnpEff's web site. For some functional effect we added a WARNING tag: it can be found for all variants modifying the first AUU, GUG or AUC codon for which an "initiator_codon_variant" or "start_retained_variant" effect has been predicted by snpEff since these codons are considered as functional start codons, even if they are differently considered in MITOMAP
  17. OMIM id: gene identifier in OMIM (ref)
  18. HGVS: variant's nomenclature according to HGVS (ref)
  19. HGNC: gene identifier in HGNC (ref)
  20. Respiratory Chain complex: Respiratory Chain Complex of the related mitochondrial protein
  21. Ensembl gene id: gene identifier from Ensembl Gene (ref)
  22. Ensembl transcript id: transcript identifier from Ensembl transcript
  23. Ensembl protein id: protein identifier from Ensembl Protein
  24. Uniprot id: protein identifier in Uniprot
  25. Uniprot name: gene symbol in Uniprot (ref)
  26. NCBI gene id: gene identifier in NCBI Gene
  27. NCBI protein id: protein identifier in NCBI Protein (ref)

    28. Conservation

  28. PhyloP 100V: 100 vertebrates Basewise conservation index by PhyloP from UCSC goldenpath hg38 (2015) (ref). [min -20, max 10] Predicted accelerated evolution: score <= 0; Conserved: score > 0
  29. PhyloP 470Way: 470 mammals Basewise conservation index by PhyloP from UCSC goldenpath hg38 (2022) (ref). [min -20, max 12] Predicted accelerated evolution: score <= 0; Conserved: score > 0
  30. PhastCons 100V: 100 vertebrates conservation index by PhastCons from UCSC goldenpath hg38 (2015) (ref). [min 0, max 1] Non-conserved: score <= 0.7; Conserved: score > 0.7 (soft threshold)
  31. PhastCons 470Way: 470 mammals Basewise conservation index by PhastCons from UCSC goldenpath hg38 (2022) (ref). [min 0, max 1] Non-conserved: score <= 0.7; Conserved: score > 0.7 (soft threshold)

    32. Pathogenicity predictors

  32. PolyPhen2: categorical prediction for PolyPhen ver. 2.2.2, HumDiv dataset (ref)
  33. PolyPhen2 score: [min 0, max 1]. Neutral: score <= 0.15; Possibly damaging: 0.15 < score <= 0.85; Probably damaging: score > 0.85
  34. SIFT: categorical prediction for SIFT ver. 5.0.3 (ref)
  35. SIFT score: [min 0, max 1]. Neutral: score > 0.05; Deleterious: score <= 0.05
  36. SIFT4G: categorical prediction (ref)
  37. SIFT4G score: [min 0, max 1]. Neutral: score > 0.05; Deleterious: score <= 0.05
  38. VEST: categorical prediction for VEST ver. 1.3 (ref)
  39. VEST score: [min 0, max 1]. Neutral: p-value > 0.05; Pathogenic: p-value <= 0.05. The score was computed using CRAVAT 3.2 (ref)
  40. VEST FDR: variant-specific false discovery rates (FDRs) assessed through CRAVAT 3.2
  41. Mitoclass.1: categorical prediction without score (ref)
  42. SNPDryad: categorical prediction (ref)
  43. SNPDryad score: [min 0, max 1]. No hard-thresholds were indicated by authors. Indicatively: Neutral: score < 0.9; Pathogenic: score >= 0.9
  44. MutationTaster: categorical prediction: "disease automatic"; "disease"; "polymorphism"; "polymorphism automatic" as retrieved from dbNSFP v4.5a (ref)
  45. MutationTaster score: [min 0, max 1]. MutationTaster p-value (MTori) as retrieved from dbNSFP v4.5a. Disease causing: p-value < 0.5; Polymorphism > 0.5
  46. MutationTaster converted rankscore: [min 0.08979, max 0.81001] MutationTaster scores converted as retrieved from dbNSFP v4.5a. If the prediction is "disease automatic" or "disease" MutationTaster converted rankscore is equal to MutationTaster score; if the prediction is "polymorphism" or "polymorphism automatic", MutationTaster converted rankscore is equal to 1-MutationTaster score"
  47. MutationTaster model: MutationTaster prediction models as retrieved from dbNSFP v4.5a
  48. MutationTaster AAE: MutationTaster predicted amino acid change as retrieved from dbNSFP v4.5a
  49. FatHmm: categorical prediction ("damaging" or "tolerated") as retrieved from dbNSFP v4.5a
  50. FatHmm score: [min -16.13, max 10.64] FATHMM scores as retrieved from dbNSFP v4.5a. Deleterious: score <= 1.5; Tolerated: score > 1.5
  51. FatHmm converted rankscore: [min 0, max 1] FATHMM scores converted as retrieved from dbNSFP v4.5a.
  52. AlphaFold: categorical prediction (Likely pathogenic, Ambiguous, or Likely benign) (ref)
  53. AlphaFold: [min 0, max 1]. 0.56 < Likely pathogenic <1.0; 0.34 < Ambiguous < 0.56; Likely benign < 0.34
  54. CADD: categorical prediction for CADD ver. 1.3 (ref)
  55. CADD raw score: [min -2.2, max 11.3] (in MitImpact)
  56. CADD phred score: [min 0, max Unlimited]. Neutral: score < 20 (soft threshold); Deleterious: score >= 20
  57. PROVEAN: categorical prediction for PROVEAN ver. 1.1 (ref)
  58. PROVEAN score: [min -14, max 14]. Neutral: score > -2.5; Deleterious: score <= -2.5 (soft threshold)
  59. MutationAssessor: categorical prediction for MutationAssessor ver. 3.0 (ref)
  60. MutationAssessor score: [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
  61. EFIN SP: score for EFIN, trained with the SwissProt dataset (ref)
  62. EFIN SP score: [min 0, max 1]. Neutral: score > 0.6; Damaging: score <= 0.6
  63. EFIN HD: score for EFIN, trained with the HumDiv dataset
  64. EFIN HD score: [min 0, max 1]. Neutral: score > 0.28; Damaging: score <= 0.28
  65. MLC: mitochondrial local constraint (ref)
  66. MLC score: [min 0, max 1]. Soft thresholds, Deleterious: score >= 0.5; Neutral: score <0.5
  67. PANTHER: categorical prediction
  68. PANTHER score: [min 0, max 1]. Neutral: score < 0.5; Disease: score >= 0.5. The score was computed using Meta-SNP (ref)
  69. PhD-SNP: categorical prediction
  70. PhD-SNP score: [min 0, max 1]. Neutral: score < 0.5; Disease: score >= 0.5. The score was computed using Meta-SNP (ref)

    71. Pathogenicity meta-predictors

  71. APOGEE1: categorical prediction [Neutral, Pathogenic] - (December 2022)
  72. APOGEE1 score: Neutral: score ≤ 0.5; Pathogenic: score > 0.5 - [min 0, max 1]
  73. APOGEE2: categorical prediction for APOGEE2 [Benign, Likely-benign, VUS, Likely-pathogenic, Pathogenic] - (December 2022)
  74. APOGEE2 score: Benign: score ≤ 0.06157; Likely-benign: 0.06157 < score ≤ 0.26529; VUS: 0.26529 < score < 0.71613; Likely-pathogenic: 0.71613 ≤ score < 0.90719; Pathogenic: score ≥ 0.90719 - [min 0, max 1]
  75. APOGEE2 probability: Benign: probability ≤ 0.001; Likely-benign: 0.001 < probability ≤ 0.1; VUS: 0.1 < probability < 0.9; Likely-pathogenic: 0.9 ≤ probability < 0.99; Pathogenic: probability ≥ 0.99 - [min 0, max 1]
  76. CAROL: categorical prediction (ref)
  77. CAROL score: [min 0, max 1]. Neutral: score < 0.98; Deleterious: score >= 0.98
  78. Condel: categorical prediction (ref)
  79. Condel score: [min 0, max 1]. Neutral: score < 0.5; Deleterious: score >= 0.5
  80. COVEC WMV: categorical prediction for the COVEC ver. 0.4 Weighted Majority Rule consensus method (ref)
  81. COVEC WMV score: [min -6, max 6]. Neutral: score < 0; Deleterious: score > 0; Inaccurate prediction: score = 0
  82. MtoolBox: categorical prediction (ref)
  83. MtoolBox DS: [min 0, max 1]. Neutral: score < 0.43; Deleterious: score >= 0.43
  84. DEOGEN2: categorical prediction ("damaging" or "tolerated") (ref)
  85. DEOGEN2 score: [min 0, max 1]. Neutral: score < 0.5; Deleterious: score >= 0.5
  86. DEOGEN2 converted rankscore: The ratio of the rank of the score over the total number of DEOGEN2 scores as retrieved from dbNSFP v4.5a
  87. Meta-SNP: categorical prediction (ref)
  88. Meta-SNP score: [min 0, max 1]. Neutral: score < 0.5; Disease: score >= 0.5

    89. Cancer-specific predictors

  89. PolyPhen2 transf: transformed PolyPhen2 categorical prediction by TransFIC ver. 1.0 (ref)
  90. PolyPhen2 transf score: [min -5, max 5]. Low impact: score <= -1; Medium impact: -1 < score < 1.5 (soft threshold); High impact: score >= 1.5 (soft threshold)
  91. SIFT transf: transformed SIFT categorical prediction by TransFIC ver. 1.0 (ref)
  92. SIFT transf score: [min -5, max 5]. Low impact: score < -1; Medium impact: -1 < score < 2 (soft threshold); High impact: score >= 2 (soft threshold)
  93. MutationAssessor transf: Transformed MutationAssessor categorical prediction by TransFIC ver. 1.0 (ref)
  94. MutationAssessor transf score: [min -5, max 5]. Low impact: score < 2; Medium impact: -1 < score < 2 (soft threshold); High impact: score >= 2 (soft threshold)
  95. CHASM: CHASM categorical rpediction, as computed by CRAVAT 3.2 (ref)
  96. CHASM p-value: variant-specific P values assessed through CRAVAT 3.2
  97. CHASM FDR: [min 0, max 1]. Variant-specific false discovery rate (FDR) assessed through CRAVAT 3.2. Neutral: FDR > 0.2; Driver: FDR <= 0.2

    98. Databases Phenotypes

  98. ClinVar id: ClinVar variation identifier (June 2024)
  99. ClinVar ALLELEID: ClinVar allele identifier
  100. Clinvar CLNDISDB: ClinVar tag-value pairs of disease database name and identifier (dbSNP-ClinVar)
  101. Clinvar CLNDN: ClinVar disease name associated with a variant
  102. Clinvar CLNSIG: ClinVar variant clinical significance
  103. MITOMAP Allele: allele description for a variant, as reported in the MITOMAP database
  104. MITOMAP Disease Clinical info: phenotypes associated with a variant in MITOMAP (August 2024)
  105. MITOMAP Disease Status: validation status for a variant in MITOMAP (refer to this for details) - (November 2023)
  106. MITOMAP Disease Hom/Het: + if a variant was found in homoplasmy (left) and/or heteroplasmy (right)
  107. MITOMAP General GenBank Freq: GenBank frequency information of a variant of the MITOMAP General variant set
  108. MITOMAP General GenBank Seqs: GenBank sequences where a variant of the MITOMAP General variant set was found
  109. MITOMAP General GenBank Curated refs: GenBank curated sequences where a variant of the MITOMAP General variant set was found
  110. MITOMAP General Variant Class: polymorphism, disease, or polymorphism,disease. It indicates whether a variant is found in the "polymorphism", "disease", or both MITOMAP data sets
  111. gnomAD AN: gnomAD 3.1 total alleles number (Info)
  112. gnomAD AC hom: Allele count of homoplasmic variants
  113. gnomAD AF hom: Allelic frequency of homoplasmic variants
  114. gnomAD AC het: Allele count of heteroplasmic variants
  115. gnomAD AF het: Allelic frequency of heteroplasmic variants
  116. gnomAD filter: Reliability flag
  117. HelixMTdb AC hom: Allele count of homoplasmic variants in HelixMTdb 20200327
  118. HelixMTdb AF hom: Allelic frequency of homoplasmic variants
  119. HelixMTdb AC het: Allele count of heteroplasmic variants
  120. HelixMTdb AF het: Allelic frequency of heteroplasmic variants
  121. HelixMTdb mean ARF: Mean Alternate Read Fraction (for heteroplasmic variants)
  122. HelixMTdb max ARF: Max Alternate Read Fraction (for heteroplasmic variants)
  123. ToMMo 54JPN AC: Allele count in the ToMMo 54KJPN database
  124. ToMMo 54JPN AF: Allelic frequency
  125. ToMMo 54JPN AN: Allelic count
  126. COSMIC 90 id: accession number for a cancer-associated variant in COSMIC ver. 90
  127. dbSNP 156 id: accession number for a variant in dbSNP ver. 156

    128. Residue interaction

  128. EVmutation: EVmutation score of pairs of amino acid variants. Scores are reported as gene: pos1aa1-pos2 aa2 → score (ref)§
  129. Site A-B InterP: predicted co-varying amino acid sites of two interacting proteins by I-COMS, using the corrected Mutual Information and Direct Coupling Analysis methods. Any pair is described as protein1:pos1-protein2:pos2 §
  130. Site A-B IntraP: predicted co-varying amino acid sites located in the same protein by I-COMS. Any pair is described as protein1:pos1-protein1: pos2§
  131. ΔΔG intraP: Free energy change of folding (ΔΔG, Kcal/mol) of pairs of co-varying amino acid variants (protein1:var1:var2). Upon selection, the righmost canvas will draw the 3D model of protein1, which will highlight both variants and will report: the ΔΔG value of both variants if considered together; the ΔΔG value for var1; the ΔΔG value for var2 (ref)#
  132. ΔΔG intraP interface: ΔΔGbind of interaction energy. Both variants of the pair belong to one of the proteins and are located in their interaction interface (protein1:protein2:PDB ID: PDB chain protein1: PDB chain protein2: var1: var2). As from above, the rightmost canvas will display: the ΔΔGbind value of both variants if considered together; the ΔΔGbind value for var1 in protein1; the ΔΔGbind value for var2 in protein1 #.
  133. ΔΔG interP: ΔΔGbind of interaction energy calculated as the energetic difference between wild-type and mutant proteins. Variants are located in different proteins (protein1:protein2:PDB ID: PDB chain protein1: PDB chain protein2: var1: var2). As from above, the rightmost canvas will display: the ΔΔGbind value of both variants if considered together; the ΔΔGbind value for var1 in protein1; the ΔΔGbind value for var2 in protein2 #.
    § Co-variation scores (i.e., EV score, mfDCA, and corrected MI) are not meant to prioritize one pair over another, since all reported pairs of co-varying variants were selected from the top scoring pairs obtained as explained in the Description page.
    # 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, as explained in the Description page.

    Compensated Pathogenic Deviations (ref, ref)

  134. Frequency: frequency of a CPD variant; it is the proportion of aligned orthologous sequences that carry a specific human pathogenic variant as wild-type amino acid on the total number of aligned sequences. In our analysis, the total number of aligned orthologous sequences is 673 (for CYB, ND6) or 674 (ND1, ND2, CO1, CO3) or 675 (all remaining genes)
  135. AA ref: reference amino acid for the CPD, considering the human protein reference sequence, as indicated in the General Info section
  136. AA alt: alternate amino acid found in the position specified by the aln pos field, within non-human mammalian species (see species name, NCBI Protein ID, and NCBI Taxon ID)
  137. Aln pos: position of the CPD within the ortholog proteins alignment; the reference is the human sequence
  138. RefSeq protein id: protein sequence identifier within the NCBI Protein Database
  139. Species name: scientific species name carrying the CPD variant as wild-type amino acid
  140. NCBI taxon id: species identifier from the NCBI Taxonomy database