TMLHE — 83 ClinVar variants
All ClinVar germline TMLHE variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 52 flagged for review →
1 Pathogenic · 2 Likely pathogenic · 1 Conflicting · 1 Benign · 13 Likely benign · 65 Uncertain significance
Full TMLHE gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 52
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 lean, ClinVar uncertain 40
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
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TMLHE p.Arg93His
Uncertain significance
Multiple submitters
epsilon-trimethyllysine hydroxylase deficiency
-
TMLHE p.Glu369Asp
Uncertain significance
Multiple submitters
epsilon-trimethyllysine hydroxylase deficiency
- TMLHE p.Pro29Ala Uncertain significance Multiple submitters
- TMLHE p.Ala25Val Uncertain significance Single submitter
- TMLHE p.Ala38Val Uncertain significance Single submitter
- TMLHE p.Ala83Val Uncertain significance Single submitter
- TMLHE p.Arg110His Uncertain significance Single submitter
- TMLHE p.Arg110Ser Uncertain significance Single submitter
- TMLHE p.Arg386His Uncertain significance Single submitter
- TMLHE p.Arg398His Uncertain significance Single submitter
- TMLHE p.Arg415Cys Uncertain significance Single submitter
- TMLHE p.Arg77Gln Uncertain significance Single submitter
-
TMLHE p.Arg93Cys
Uncertain significance
Single submitter
isolated cerebellar hypoplasia/agenesis
- TMLHE p.Asn412Ser Uncertain significance Single submitter
- TMLHE p.Asp231Val Uncertain significance Single submitter
- TMLHE p.Asp244Asn Uncertain significance Single submitter
- TMLHE p.Asp58Asn Uncertain significance Single submitter
- TMLHE p.Cys393Tyr Uncertain significance Single submitter
- TMLHE p.Gln141Lys Uncertain significance Single submitter
- TMLHE p.Gln159Glu Uncertain significance Single submitter
- TMLHE p.Gln280Arg Uncertain significance Single submitter
- TMLHE p.Gly19Glu Uncertain significance Single submitter
- TMLHE p.Gly396Ser Uncertain significance Single submitter
- TMLHE p.His124Arg Uncertain significance Single submitter
- TMLHE p.Ile150Leu Uncertain significance Single submitter
- TMLHE p.Ile313Phe Uncertain significance Single submitter
- TMLHE p.Ile313Thr Uncertain significance Single submitter
- TMLHE p.Leu405Val Uncertain significance Single submitter
- TMLHE p.Phe394Leu Uncertain significance Single submitter
- TMLHE p.Pro197His Uncertain significance Single submitter
-
TMLHE p.Ser164Leu
Uncertain significance
Single submitter
epsilon-trimethyllysine hydroxylase deficiency
- TMLHE p.Ser84Leu Uncertain significance Single submitter
- TMLHE p.Ser88Phe Uncertain significance Single submitter
- TMLHE p.Thr198Ser Uncertain significance Single submitter
-
TMLHE p.Thr224Ile
Uncertain significance
Single submitter
TMLHE-related disorder
- TMLHE p.Thr395Ile Uncertain significance Single submitter
- TMLHE p.Tyr23His Uncertain significance Single submitter
- TMLHE p.Val74Ile Uncertain significance Single submitter
-
TMLHE p.Arg81Cys
Uncertain significance
No assertion criteria
TMLHE-related disorder
-
TMLHE p.Trp2Cys
Uncertain significance
No assertion criteria
epsilon-trimethyllysine hydroxylase deficiency
Predictors split 12
The independent predictors disagree with each other — read with care.
-
TMLHE p.Glu175Lys
Uncertain significance
Multiple submitters
epsilon-trimethyllysine hydroxylase deficiency
-
TMLHE p.Thr265Ile
Uncertain significance
Multiple submitters
epsilon-trimethyllysine hydroxylase deficiency
- TMLHE p.Ala233Val Uncertain significance Single submitter
- TMLHE p.Ala277Val Uncertain significance Single submitter
- TMLHE p.Arg219Gly Uncertain significance Single submitter
- TMLHE p.Gln280His Uncertain significance Single submitter
- TMLHE p.Ile302Thr Uncertain significance Single submitter
- TMLHE p.Leu151Val Uncertain significance Single submitter
- TMLHE p.Lys204Asn Uncertain significance Single submitter
- TMLHE p.Ser210Asn Uncertain significance Single submitter
- TMLHE p.Tyr187Cys Uncertain significance Single submitter
- TMLHE p.Val295Met Uncertain significance Single submitter
All TMLHE variants
Pathogenic 1
- p.Ile321fs Multiple submitters epsilon-trimethyllysine hydroxylase deficiency
Likely pathogenic 2
- p.Trp75Ter Single submitter epsilon-trimethyllysine hydroxylase deficiency
- c.638+2del No assertion criteria epsilon-trimethyllysine hydroxylase deficiency
Conflicting classifications of pathogenicity 1
- c.359-2A>G Single submitter epsilon-trimethyllysine hydroxylase deficiency
Benign 1
- p.Phe191= Single submitter
Likely benign 13
- p.Gly266= Multiple submitters
- p.Leu111= Multiple submitters
- p.Thr235Asn Multiple submitters
- c.1135-16_1135-14del Single submitter
- p.Arg241Gln Single submitter
- p.Asn174= Single submitter
- p.Asp304Asn Single submitter
- p.Gly20Arg Single submitter
- p.Phe223= Single submitter
- p.Ser164= Single submitter
- p.Thr50Asn Single submitter
- p.Val100= Single submitter
- p.Ile321= No assertion criteria TMLHE-related disorder
Uncertain significance 65
- p.Arg77Ter Multiple submitters intellectual disability
- p.Arg93His Multiple submitters epsilon-trimethyllysine hydroxylase deficiency ⚠
- p.Glu175Lys Multiple submitters epsilon-trimethyllysine hydroxylase deficiency ⚠
- p.Glu369Asp Multiple submitters epsilon-trimethyllysine hydroxylase deficiency ⚠
- p.Pro29Ala Multiple submitters ⚠
- p.Thr265Ile Multiple submitters epsilon-trimethyllysine hydroxylase deficiency ⚠
- p.Trp53Ter Multiple submitters epsilon-trimethyllysine hydroxylase deficiency
- c.638+83_995+2127del Single submitter epsilon-trimethyllysine hydroxylase deficiency
- c.995+2T>C Single submitter epsilon-trimethyllysine hydroxylase deficiency
- p.Ala233Val Single submitter ⚠
- p.Ala25Val Single submitter ⚠
- p.Ala277Val Single submitter ⚠
- p.Ala38Val Single submitter ⚠
- p.Ala83Val Single submitter ⚠
- p.Arg110His Single submitter ⚠
- p.Arg110Ser Single submitter ⚠
- p.Arg219Gly Single submitter ⚠
- p.Arg386His Single submitter ⚠
- p.Arg398His Single submitter ⚠
- p.Arg415Cys Single submitter ⚠
- p.Arg77Gln Single submitter ⚠
- p.Arg93Cys Single submitter isolated cerebellar hypoplasia/agenesis ⚠
- p.Asn310fs Single submitter epsilon-trimethyllysine hydroxylase deficiency
- p.Asn412Ser Single submitter ⚠
- p.Asp231= Single submitter
- p.Asp231Val Single submitter ⚠
- p.Asp244Asn Single submitter ⚠
- p.Asp58Asn Single submitter ⚠
- p.Cys393Tyr Single submitter ⚠
- p.Gln141Lys Single submitter ⚠
- p.Gln159Glu Single submitter ⚠
- p.Gln280Arg Single submitter ⚠
- p.Gln280His Single submitter ⚠
- p.Gln283Pro Single submitter
- p.Gln399Ter Single submitter
- p.Glu392Gln Single submitter
- p.Gly19Glu Single submitter ⚠
- p.Gly396Ser Single submitter ⚠
- p.His124Arg Single submitter ⚠
- p.Ile150Leu Single submitter ⚠
- p.Ile302Thr Single submitter ⚠
- p.Ile313Phe Single submitter ⚠
- p.Ile313Thr Single submitter ⚠
- p.Leu151Val Single submitter ⚠
- p.Leu405Val Single submitter ⚠
- p.Lys204Asn Single submitter ⚠
- p.Lys236fs Single submitter epsilon-trimethyllysine hydroxylase deficiency
- p.Lys236Ter Single submitter
- p.Phe394Leu Single submitter ⚠
- p.Pro197His Single submitter ⚠
- p.Ser164Leu Single submitter epsilon-trimethyllysine hydroxylase deficiency ⚠
- p.Ser210Asn Single submitter ⚠
- p.Ser84Leu Single submitter ⚠
- p.Ser88Phe Single submitter ⚠
- p.Thr198Ser Single submitter ⚠
- p.Thr224Ile Single submitter TMLHE-related disorder ⚠
- p.Thr395Ile Single submitter ⚠
- p.Trp2Ter Single submitter
- p.Tyr187Cys Single submitter ⚠
- p.Tyr23His Single submitter ⚠
- p.Val295Met Single submitter ⚠
- p.Val74Ile Single submitter ⚠
- c.639-10_758+10del No assertion criteria epsilon-trimethyllysine hydroxylase deficiency
- p.Arg81Cys No assertion criteria TMLHE-related disorder ⚠
- p.Trp2Cys No assertion criteria epsilon-trimethyllysine hydroxylase deficiency ⚠