Sugi Variant

Sugi Variant/TK2

TK2 — 540 ClinVar variants

All ClinVar germline TK2 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 134 flagged for review →

40 Pathogenic · 19 Pathogenic/Likely pathogenic · 29 Likely pathogenic · 32 Conflicting · 32 Benign · 3 Benign/Likely benign · 209 Likely benign · 176 Uncertain significance

Full TK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 134

Variants where the independent computational evidence doesn't line up with the clinical picture — a QC signal for a second look, not a reclassification.

Predictors vs ClinVar 8

ClinVar calls these pathogenic, but the computational predictors lean tolerated — the highest-value review flag.

Predictors agree, ClinVar conflicts 18

ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.

Predictors lean, ClinVar uncertain 82

ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.

Predictors split 26

The independent predictors disagree with each other — read with care.

All TK2 variants

Pathogenic 40

Pathogenic/Likely pathogenic 19

  • c.125-1_127del Multiple submitters
  • c.156+2T>C Multiple submitters Fetal anomalies with a likely genetic cause
  • c.157-2A>G Multiple submitters mitochondrial disease
  • c.536_538+8del Multiple submitters mitochondrial disease
  • p.Ala139Thr Multiple submitters Autosomal recessive TK2-related disorders
  • p.Ala139Val Multiple submitters TK2-related disorder
  • p.Ala230fs Multiple submitters
  • p.Arg104Cys Multiple submitters mitochondrial disease
  • p.Arg130Gln Multiple submitters mitochondrial DNA depletion syndrome ⚠
  • p.Arg130Trp Multiple submitters mitochondrial DNA depletion syndrome
  • p.Arg183Gly Multiple submitters mitochondrial disease
  • p.Asn58Ser Multiple submitters Mitochondrial DNA depletion syndrome 2, myopathic form
  • p.Leu182fs Multiple submitters mitochondrial disease
  • p.Leu215Pro Multiple submitters mitochondrial disease
  • p.Lys202del Multiple submitters mitochondrial DNA depletion syndrome
  • p.Met117Val Multiple submitters mitochondrial disease ⚠
  • p.Thr64Met Multiple submitters progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3
  • p.Tyr148fs Multiple submitters mitochondrial DNA depletion syndrome, myopathic form
  • p.Tyr208Cys Multiple submitters progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3

Likely pathogenic 29

Conflicting classifications of pathogenicity 32

  • c.125-13C>T Single submitter mitochondrial DNA depletion syndrome, myopathic form
  • c.699+6_699+9del Single submitter mitochondrial DNA depletion syndrome, myopathic form
  • p.Ala139Ser Single submitter ⚠
  • p.Arg104His Single submitter mitochondrial disease
  • p.Arg123Gly Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3 ⚠
  • p.Arg183Gln Single submitter Inborn genetic diseases ⚠
  • p.Arg196Ser Single submitter mitochondrial DNA depletion syndrome, myopathic form ⚠
  • p.Arg90Cys Single submitter mitochondrial disease ⚠
  • p.Asn93Ser Single submitter mitochondrial disease ⚠
  • p.Asp166Val Single submitter mitochondrial disease ⚠
  • p.Asp173= Single submitter mitochondrial DNA depletion syndrome, myopathic form
  • p.Asp42_Lys43delinsGlu Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3
  • p.Cys54Tyr Single submitter mitochondrial disease ⚠
  • p.Gly57Ser Single submitter mitochondrial disease ⚠
  • p.His100= Single submitter mitochondrial DNA depletion syndrome, myopathic form
  • p.Ile255Val Single submitter mitochondrial DNA depletion syndrome, myopathic form
  • p.Leu115Phe Single submitter mitochondrial disease ⚠
  • p.Leu220Pro Single submitter mitochondrial disease ⚠
  • p.Met172Val Single submitter ⚠
  • p.Phe70Ser Single submitter mitochondrial disease ⚠
  • p.Pro186Arg Single submitter mitochondrial DNA depletion syndrome, myopathic form ⚠
  • p.Pro227Leu Single submitter Inborn genetic diseases ⚠
  • p.Pro231Leu Single submitter mitochondrial DNA depletion syndrome, myopathic form ⚠
  • p.Pro41His Single submitter mitochondrial DNA depletion syndrome, myopathic form ⚠
  • p.Ser138= Single submitter mitochondrial DNA depletion syndrome, myopathic form
  • p.Ser61Gly Single submitter ⚠
  • p.Thr111Ala Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3 ⚠
  • p.Trp219Arg Single submitter mitochondrial disease ⚠
  • p.Tyr158Cys Single submitter mitochondrial DNA depletion syndrome, myopathic form ⚠
  • p.Val113Glu Single submitter mitochondrial disease ⚠
  • p.Val174Leu Single submitter ⚠
  • p.Val83Ala Single submitter ⚠

Benign 32

  • c.124+136A>G Multiple submitters
  • c.124+194T>C Multiple submitters
  • c.124+223C>G Multiple submitters
  • c.125-116G>A Multiple submitters mitochondrial disease
  • c.156+15T>C Multiple submitters mitochondrial DNA depletion syndrome, myopathic form
  • c.157-12G>A Multiple submitters mitochondrial DNA depletion syndrome, myopathic form
  • c.286-120T>C Multiple submitters
  • c.539-176G>A Multiple submitters
  • c.539-20A>G Multiple submitters
  • c.619-53A>G Multiple submitters progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3
  • c.619-63C>G Multiple submitters mitochondrial disease
  • c.700-13G>A Multiple submitters mitochondrial DNA depletion syndrome, myopathic form
  • c.700-60G>A Multiple submitters
  • c.-30C>G Multiple submitters progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3
  • c.-38A>G Multiple submitters progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3
  • c.-517T>A Multiple submitters
  • c.*2221T>C Multiple submitters mitochondrial DNA depletion syndrome, myopathic form
  • c.*2419C>T Multiple submitters mitochondrial DNA depletion syndrome, myopathic form
  • c.*2914C>T Multiple submitters mitochondrial DNA depletion syndrome, myopathic form
  • c.*3786C>T Multiple submitters mitochondrial DNA depletion syndrome, myopathic form
  • c.*765T>C Multiple submitters mitochondrial DNA depletion syndrome, myopathic form
  • c.156+15dup Single submitter
  • c.156+742G>A Single submitter mitochondrial disease
  • c.156+836G>A Single submitter mitochondrial disease
  • c.157-240G>A Single submitter
  • c.157-6del Single submitter
  • c.375+227T>A Single submitter
  • c.376-260C>T Single submitter
  • c.449+130C>T Single submitter
  • c.619-5G>C Single submitter
  • c.*1959G>A Single submitter mitochondrial DNA depletion syndrome, myopathic form
  • c.*2450A>G Single submitter mitochondrial DNA depletion syndrome, myopathic form

Benign/Likely benign 3

  • c.231+10C>T Multiple submitters mitochondrial DNA depletion syndrome, myopathic form
  • c.449+14A>C Multiple submitters mitochondrial DNA depletion syndrome, myopathic form
  • p.Arg192= Multiple submitters mitochondrial DNA depletion syndrome, myopathic form

Likely benign 209

Uncertain significance 176