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6277 (G > A)

General info

Mitimpact ID
MI.2677
Chr
chrM
Start
6277
Ref
G
Alt
A
Gene symbol
MT-CO1 Extended gene annotation
Gene position
374
Gene start
5904
Gene end
7445
Gene strand
+
Codon substitution
GGT/GAT
AA pos
125
AA ref
G
AA alt
D
Functional effect
missense
OMIM ID
516030
HGVS
NC_012920.1:g.6277G>A
HGNC ID
7419
RC complex
IV
Ensembl gene ID
ENSG00000198804
Ensembl protein ID
ENSP00000354499
Ensembl transcript ID
ENST00000361624
Uniprot ID
P00395
Uniprot name
COX1_HUMAN
Ncbi gene ID
4512
Ncbi protein ID
YP_003024028.1
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Conservation

PhyloP 100v
9.457 Conservation Score
PhyloP 470way
0.458 Conservation Score
PhastCons 100v
1 Conservation Score
PhastCons 470way
0.869 Conservation Score

Pathogenicity predictors

PolyPhen2
Probably damaging Score and details of the predictor
SIFT
Deleterious Score and details of the predictor
SIFT4G
Damaging Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Damaging Score and details of the predictor
SNPDryad
Pathogenic Score and details of the predictor
MutationTaster
Disease automatic Score and details of the predictor
fathmm
Tolerated Score and details of the predictor
AlphaMissense
Likely pathogenic Score and details of the predictor
CADD
Deleterious Score and details of the predictor
PROVEAN
Damaging Score and details of the predictor
Mutation Assessor
High Score and details of the predictor
EFIN SP
Damaging Score and details of the predictor
EFIN HD
Damaging Score and details of the predictor
MLC
Deleterious Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Pathogenic Score and details of the meta-predictor
APOGEE2
Likely-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
MtoolBox
Deleterious Score and details of the meta-predictor
DEOGEN2
Tolerated Score and details of the meta-predictor
Meta SNP
.

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 Frequencies and Phenotypes

Clinvar ID
9672
Clinvar ALLELEID
24711
Clinvar CLNDISDB
Mondo:mondo:0023113, medgen:cn280943
Clinvar CLNDN
Familial colorectal cancer
Clinvar CLNSIG
Pathogenic
MITOMAP Allele
6277G>A
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease Hom/Het
./.
MITOMAP General GenBank Freq
.
MITOMAP General GenBank Seqs
.
MITOMAP General GenBank Curated refs
.
MITOMAP Variant Class
.
Gnomad AN
56431
Gnomad AC hom
0
Gnomad AF hom
0.0
Gnomad AC het
0
Gnomad AF het
0.0
Gnomad filter
Npg
HelixMTdb AC hom
0
HelixMTdb AF hom
0.0
HelixMTdb AC het
.
HelixMTdb AF het
0.0
HelixMTdb mean ARF
0.0
HelixMTdb max ARF
.
ToMMo JPN54K AC
.
ToMMo JPN54K AF
.
ToMMo JPN54K AN
.
COSMIC 90
.
dbSNP 156
rs281865417

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
.

6277 (G > C)

General info

Mitimpact ID
MI.2678
Chr
chrM
Start
6277
Ref
G
Alt
C
Gene symbol
MT-CO1 Extended gene annotation
Gene position
374
Gene start
5904
Gene end
7445
Gene strand
+
Codon substitution
GGT/GCT
AA pos
125
AA ref
G
AA alt
A
Functional effect
missense
OMIM ID
516030
HGVS
NC_012920.1:g.6277G>C
HGNC ID
7419
RC complex
IV
Ensembl gene ID
ENSG00000198804
Ensembl protein ID
ENSP00000354499
Ensembl transcript ID
ENST00000361624
Uniprot ID
P00395
Uniprot name
COX1_HUMAN
Ncbi gene ID
4512
Ncbi protein ID
YP_003024028.1
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
9.457 Conservation Score
PhyloP 470way
0.458 Conservation Score
PhastCons 100v
1 Conservation Score
PhastCons 470way
0.869 Conservation Score

Pathogenicity predictors

PolyPhen2
Probably damaging Score and details of the predictor
SIFT
Deleterious Score and details of the predictor
SIFT4G
Damaging Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Damaging Score and details of the predictor
SNPDryad
Neutral Score and details of the predictor
MutationTaster
Disease Score and details of the predictor
fathmm
Tolerated Score and details of the predictor
AlphaMissense
Likely pathogenic Score and details of the predictor
CADD
Deleterious Score and details of the predictor
PROVEAN
Damaging Score and details of the predictor
Mutation Assessor
High Score and details of the predictor
EFIN SP
Damaging Score and details of the predictor
EFIN HD
Damaging Score and details of the predictor
MLC
Deleterious Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Pathogenic Score and details of the meta-predictor
APOGEE2
Vus 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
MtoolBox
Deleterious Score and details of the meta-predictor
DEOGEN2
Tolerated Score and details of the meta-predictor
Meta SNP
.

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 Frequencies and Phenotypes

Clinvar ID
.
Clinvar ALLELEID
.
Clinvar CLNDISDB
.
Clinvar CLNDN
.
Clinvar CLNSIG
.
MITOMAP Allele
6277G>C
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease Hom/Het
./.
MITOMAP General GenBank Freq
.
MITOMAP General GenBank Seqs
.
MITOMAP General GenBank Curated refs
.
MITOMAP Variant Class
.
Gnomad AN
0
Gnomad AC hom
0
Gnomad AF hom
0.0
Gnomad AC het
.
Gnomad AF het
.
Gnomad filter
.
HelixMTdb AC hom
0
HelixMTdb AF hom
0.0
HelixMTdb AC het
.
HelixMTdb AF het
0.0
HelixMTdb mean ARF
0.0
HelixMTdb max ARF
.
ToMMo JPN54K AC
.
ToMMo JPN54K AF
.
ToMMo JPN54K AN
.
COSMIC 90
.
dbSNP 156
.

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
.

6277 (G > T)

General info

Mitimpact ID
MI.2676
Chr
chrM
Start
6277
Ref
G
Alt
T
Gene symbol
MT-CO1 Extended gene annotation
Gene position
374
Gene start
5904
Gene end
7445
Gene strand
+
Codon substitution
GGT/GTT
AA pos
125
AA ref
G
AA alt
V
Functional effect
missense
OMIM ID
516030
HGVS
NC_012920.1:g.6277G>T
HGNC ID
7419
RC complex
IV
Ensembl gene ID
ENSG00000198804
Ensembl protein ID
ENSP00000354499
Ensembl transcript ID
ENST00000361624
Uniprot ID
P00395
Uniprot name
COX1_HUMAN
Ncbi gene ID
4512
Ncbi protein ID
YP_003024028.1
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
9.457 Conservation Score
PhyloP 470way
0.458 Conservation Score
PhastCons 100v
1 Conservation Score
PhastCons 470way
0.869 Conservation Score

Pathogenicity predictors

PolyPhen2
Probably damaging Score and details of the predictor
SIFT
Deleterious Score and details of the predictor
SIFT4G
Damaging Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Damaging Score and details of the predictor
SNPDryad
Pathogenic Score and details of the predictor
MutationTaster
Disease Score and details of the predictor
fathmm
Tolerated Score and details of the predictor
AlphaMissense
Likely pathogenic Score and details of the predictor
CADD
Deleterious Score and details of the predictor
PROVEAN
Damaging Score and details of the predictor
Mutation Assessor
High Score and details of the predictor
EFIN SP
Damaging Score and details of the predictor
EFIN HD
Damaging Score and details of the predictor
MLC
Deleterious Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Pathogenic Score and details of the meta-predictor
APOGEE2
Vus+ 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
MtoolBox
Deleterious Score and details of the meta-predictor
DEOGEN2
Tolerated Score and details of the meta-predictor
Meta SNP
.

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 Frequencies and Phenotypes

Clinvar ID
.
Clinvar ALLELEID
.
Clinvar CLNDISDB
.
Clinvar CLNDN
.
Clinvar CLNSIG
.
MITOMAP Allele
6277G>T
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease Hom/Het
./.
MITOMAP General GenBank Freq
.
MITOMAP General GenBank Seqs
.
MITOMAP General GenBank Curated refs
.
MITOMAP Variant Class
.
Gnomad AN
0
Gnomad AC hom
0
Gnomad AF hom
0.0
Gnomad AC het
.
Gnomad AF het
.
Gnomad filter
.
HelixMTdb AC hom
0
HelixMTdb AF hom
0.0
HelixMTdb AC het
.
HelixMTdb AF het
0.0
HelixMTdb mean ARF
0.0
HelixMTdb max ARF
.
ToMMo JPN54K AC
.
ToMMo JPN54K AF
.
ToMMo JPN54K AN
.
COSMIC 90
.
dbSNP 156
.

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
.
~ 6277 (G/A) 6277 (G/C) 6277 (G/T)
~ 6277 (GGT/GAT) 6277 (GGT/GCT) 6277 (GGT/GTT)
MitImpact id MI.2677 MI.2678 MI.2676
Chr chrM chrM chrM
Start 6277 6277 6277
Ref G G G
Alt A C T
Gene symbol MT-CO1 MT-CO1 MT-CO1
Extended annotation mitochondrially encoded cytochrome c oxidase I mitochondrially encoded cytochrome c oxidase I mitochondrially encoded cytochrome c oxidase I
Gene position 374 374 374
Gene start 5904 5904 5904
Gene end 7445 7445 7445
Gene strand + + +
Codon substitution GGT/GAT GGT/GCT GGT/GTT
AA position 125 125 125
AA ref G G G
AA alt D A V
Functional effect general missense missense missense
Functional effect detailed missense missense missense
OMIM id 516030 516030 516030
HGVS NC_012920.1:g.6277G>A NC_012920.1:g.6277G>C NC_012920.1:g.6277G>T
HGNC id 7419 7419 7419
Respiratory Chain complex IV IV IV
Ensembl gene id ENSG00000198804 ENSG00000198804 ENSG00000198804
Ensembl transcript id ENST00000361624 ENST00000361624 ENST00000361624
Ensembl protein id ENSP00000354499 ENSP00000354499 ENSP00000354499
Uniprot id P00395 P00395 P00395
Uniprot name COX1_HUMAN COX1_HUMAN COX1_HUMAN
Ncbi gene id 4512 4512 4512
Ncbi protein id YP_003024028.1 YP_003024028.1 YP_003024028.1
PhyloP 100V 9.457 9.457 9.457
PhyloP 470Way 0.458 0.458 0.458
PhastCons 100V 1 1 1
PhastCons 470Way 0.869 0.869 0.869
PolyPhen2 probably_damaging probably_damaging probably_damaging
PolyPhen2 score 1.0 1.0 1.0
SIFT deleterious deleterious deleterious
SIFT score 0.0 0.0 0.0
SIFT4G Damaging Damaging Damaging
SIFT4G score 0.0 0.0 0.0
VEST Neutral Neutral Neutral
VEST pvalue 0.18 0.25 0.18
VEST FDR 0.55 0.55 0.55
Mitoclass.1 damaging damaging damaging
SNPDryad Pathogenic Neutral Pathogenic
SNPDryad score 0.97 0.64 0.93
MutationTaster Disease automatic Disease Disease
MutationTaster score 1.0 1.0 1.0
MutationTaster converted rankscore 0.81001 0.81001 0.81001
MutationTaster model simple_aae simple_aae simple_aae
MutationTaster AAE G125D G125A G125V
fathmm Tolerated Tolerated Tolerated
fathmm score 2.53 2.51 2.49
fathmm converted rankscore 0.14038 0.14284 0.14531
AlphaMissense likely_pathogenic likely_pathogenic likely_pathogenic
AlphaMissense score 0.996 0.9507 0.9915
CADD Deleterious Deleterious Deleterious
CADD score 3.725223 3.004478 3.696061
CADD phred 23.3 22.2 23.3
PROVEAN Damaging Damaging Damaging
PROVEAN score -5.81 -4.98 -7.47
MutationAssessor high high high
MutationAssessor score 4.66 4.455 5.7
EFIN SP Damaging Damaging Damaging
EFIN SP score 0.284 0.6 0.496
EFIN HD Damaging Damaging Damaging
EFIN HD score 0.028 0.056 0.04
MLC Deleterious Deleterious Deleterious
MLC score 0.59750136 0.59750136 0.59750136
PANTHER score . . .
PhD-SNP score . . .
APOGEE1 Pathogenic Pathogenic Pathogenic
APOGEE1 score 0.85 0.51 0.62
APOGEE2 Likely-pathogenic VUS VUS+
APOGEE2 score 0.794688817191833 0.526818641995807 0.594128273612631
CAROL deleterious deleterious deleterious
CAROL score 1.0 1.0 1.0
Condel neutral neutral neutral
Condel score 0.0 0.0 0.0
COVEC WMV deleterious deleterious deleterious
COVEC WMV score 6 6 6
MtoolBox deleterious deleterious deleterious
MtoolBox DS 0.88 0.83 0.85
DEOGEN2 Tolerated Tolerated Tolerated
DEOGEN2 score 0.499014 0.356428 0.498472
DEOGEN2 converted rankscore 0.82021 0.72329 0.81989
Meta-SNP . . .
Meta-SNP score . . .
PolyPhen2 transf low impact low impact low impact
PolyPhen2 transf score -3.58 -3.58 -3.58
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 3.29 2.89 3.79
CHASM Neutral Neutral Neutral
CHASM pvalue 0.41 0.7 0.55
CHASM FDR 0.9 0.9 0.9
ClinVar id 9672.0 . .
ClinVar Allele id 24711.0 . .
ClinVar CLNDISDB MONDO:MONDO:0023113,MedGen:CN280943 . .
ClinVar CLNDN Familial_colorectal_cancer . .
ClinVar CLNSIG Pathogenic . .
MITOMAP Disease Clinical info . . .
MITOMAP Disease Status . . .
MITOMAP Disease Hom/Het ./. ./. ./.
MITOMAP General GenBank Freq . . .
MITOMAP General GenBank Seqs . . .
MITOMAP General Curated refs . . .
MITOMAP Variant Class . . .
gnomAD 3.1 AN 56431.0 . .
gnomAD 3.1 AC Homo 0.0 . .
gnomAD 3.1 AF Hom 0.0 . .
gnomAD 3.1 AC Het 0.0 . .
gnomAD 3.1 AF Het 0.0 . .
gnomAD 3.1 filter npg . .
HelixMTdb AC Hom . . .
HelixMTdb AF Hom . . .
HelixMTdb AC Het . . .
HelixMTdb AF Het . . .
HelixMTdb mean ARF . . .
HelixMTdb max ARF . . .
ToMMo 54KJPN AC . . .
ToMMo 54KJPN AF . . .
ToMMo 54KJPN AN . . .
COSMIC 90 . . .
dbSNP 156 id rs281865417 . .
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.
0
Details:
0
Score:  
0
  [min -20, max 10]
  • Predicted accelerated evolution:  score <= 0
  • Conserved:  score > 0
Score:  
0
  [min -20, max 12]
  • Predicted accelerated evolution:  score <= 0
  • Conserved:  score > 0
Score:  
0
  [min 0, max 1]
  • Non-conserved:  score <= 0.7
  • Conserved:  score > 0.7 (soft threshold)
Score:  
0
  [min 0, max 1]
  • Non-conserved:  score <= 0.7
  • Conserved:  score > 0.7 (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 0, max 1]
  • Neutral:  score > 0.05
  • Deleterious:  score <= 0.05
Score:  
0
  [min -16.13, max 10.64]
  • Neutral:  score > 1.5
  • Deleterious:  score <= 1.5
Score:  
0
  [min 0.0, max 1.0]
  • Likely benign:  score <= 0.34
  • Ambiguous:  0.34 < score < 0.56
  • Likely pathogenic:  score >= 0.56
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 Unlimited]
  • Neutral:  score < 20 (soft threshold)
  • Deleterious:  score >= 20
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5 (soft threshold)
  • Deleterious:  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
Pathogenicity score:  
0
  [min 0, max 1]
  • Neutral:  score ≤ 0.5
  • Pathogenic:  score > 0.5


Pathogenicity score for this variant:  
0
  [min 0, max 1]
ACMG-AMP curations for mitochondrial variants should use the raw scores. Standalone probabilities are shown below:
  • Benign:  score ≤ 0.062 (prob. ≤ 0.001)
  • Likely-benign:  0.062 < score ≤ 0.265 (0.001 < prob. ≤ 0.1)
  • Low-scoring VUS (VUS-):  0.265 < score ≤ 0.396 (0.1 < prob. ≤ 0.33)
  • VUS:  0.396 < score ≤ 0.544 (0.33 < prob. ≤ 0.66)
  • High-scoring VUS (VUS+):  0.544 < score < 0.716 (0.66 < prob. < 0.9)
  • Likely-pathogenic:  0.716 ≤ score < 0.907 (0.9 ≤ prob. < 0.99)
  • Pathogenic:  score ≥ 0.907 (prob. ≥ 0.99)
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