Trifunctional Protein (TFP) Deficiency 

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HADHB

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Introduction

The HADHB gene, hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta, is located on chromosome 2p23.3 and has 16 exons spanning ~475kb (1). It encodes the 475 amino acid protein beta subunit of the mitochondrial trifunctional protein (2), which catalyzes the last three steps of mitochondrial beta-oxidation of long chain fatty acids (3-5). Among the enzymes involved in this pathway, the trifunctional enzyme exhibits specificity for long-chain fatty acids (2).

Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities, while the trifunctional enzyme subunit beta/HADHB described here bears the 3-ketoacyl-CoA thiolase activity (3-5).The protein is expressed in heart, duodenum and other tissues(6). The encoded protein can also bind RNA and decreases the stability of some mRNAs (2).

More than 102 disease-causing variants in the HADHB gene have been identified in patients and are represented in this database. The variants occur across the entire length of the gene and include frameshift, splice site, copy-number, nonsense and missense variants (7).

Variant List

To see more information, click on the Variant in the table. Hover on the Variant in the table to see its location on the gene . For more information on table headers, HGVS nomenclature, and ACMG classification please use the following links here.

Gene Structure
Variant_IDVariantAmino_Acid_ChangeProtein DomainDisplay ACMG CallACMG_Call_Last_Revised_DateVariant_TypeEffect_Typegene_symbolTimes_Observed_RangePMIDArticle_CountPhenotypeDisease subtypeVariant_StartLocation
HADHB_0001c.(-9+1_-8-1)_(109+1_110-1)delp.?Not SpecifiedPathogenic03/01/2023HADHB<3283924171Hypoglycemia, RhabdomyolysisTFP
HADHB_0002c.210-?_354+?delDeletion (Exons 5-6)Not SpecifiedPathogenic05/16/2023HADHB<30TFP210
HADHB_0003c.1150-?_1389+?delDeletion (Exons 14-15)Not SpecifiedLikely Pathogenic05/16/2023HADHB<30TFP1150
HADHB_0004c.-8-2780_109+2924delIntronicNot SpecifiedPathogenic03/01/2023Copy Number LossHADHB<3215496241TFPExon 2-3, Intron 1-3
HADHB_0005c.18C>Ap.Tyr6*Not SpecifiedPathogenic03/01/2023SNVNonsenseHADHB<3353839651Abnormality of metabolism/homeostasis, CardiomyopathyTFP18Exon 2
HADHB_0006c.88_91delp.Gln31Tyrfs*15Not SpecifiedPathogenic03/01/2023DeletionFrameshiftHADHB<3206598131Cardiomyopathy, Hypoglycemia, MyopathyTFP88Exon 3
HADHB_0007c.106C>Tp.Pro36SerNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<3236651941TFP106Exon 3
HADHB_0008c.166G>Tp.Val56LeuNot SpecifiedUncertain Significance05/16/2023SNVMissenseHADHB<30TFP166Exon 4
HADHB_0009c.170_172delp.Val57delNot SpecifiedUncertain Significance03/01/2023DeletionDeletionHADHB<3215496241TFP170Exon 4
HADHB_0010c.176G>Ap.Gly59AspNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<3127547061Cardiomyopathy, Myopathy, Peripheral neuropathyTFP176Exon 4
HADHB_0011c.181C>Tp.Arg61CysNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB6-1012754706, 31527676, 353839653Abnormality of metabolism/homeostasis, Cardiomyopathy, Dilated cardiomyopathy, Hellp syndrome, Hypoglycemia, Myopathy, Peripheral neuropathyTFP181Exon 4
HADHB_0012c.182G>Ap.Arg61HisNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB3-512754706, 15617873, 16423905, 35383965, 35782614, 865128263-hydroxydicarboxylic aciduria, Abnormality of metabolism/homeostasis, Cardiac-other, Cardiomyopathy, Decreased body weight, Decreased liver function, Feeding difficulties, Hyaline membrane disease of the lungs, Hyperammonemia, Hypoglycemia, Hypotonia, Intestinal pseudo-obstruction, Muscle weakness, Myopathy, Peripheral neuropathy, Pulmonary/respiratory, Respiratory tract infection, Rhabdomyolysis, VomitingTFP182Exon 4
HADHB_0013c.184A>Gp.Thr62AlaNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<3243791011Arrhythmia, Elevated circulating creatine kinase concentration, Fever, Herpetic gingivostomatitis, Hypotonia, Lethargy, Malaise/fatigue, Muscle weakness, Poor feeding, RhabdomyolysisTFP184Exon 4
HADHB_0014c.206C>Tp.Thr69IleNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<3301937511TFP206Exon 4
HADHB_0015c.209+1G>CIntronicNot SpecifiedPathogenic03/01/2023SNVSplice donorHADHB6-1021549624, 28685493, 33123633, 35383965, 354037305Abnormal gait, Abnormality of metabolism/homeostasis, Areflexia, Arrhythmia, Cardiac-other, Cardiomyopathy, Diarrhea, Difficulty moving arms, Difficulty speaking, Difficulty swallowing, Dyspnoea, Elevated circulating creatine kinase concentration, Fever, Gastrointestinal-other, Hypoesthesia, Hypoparathyroidism, Hypotonia, Loss of balance, Muscle spasm, Muscle weakness, Myalgia, Pain, Peripheral neuropathy, Pes cavus, Rhabdomyolysis, Sensory deficits, Shuddering attacks, Upper quadrant abdominal tenderness, Urine discoloration, VomitingTFP209Intron 4
HADHB_0016c.210-1G>CIntronicNot SpecifiedPathogenic03/01/2023SNVSplice acceptorHADHB3-5243140341Abnormal motor nerve conduction velocities, Absent deep tendon reflexes, Atrophy, Atrophy of bilateral distal muscles, Bilateral foot drop, Distal muscle weakness, Disturbed vibration and position senses, Gait disability, Gait disturbance, Loss of sensory and tendon reflexes, Lower limb muscle weakness, Muscle weakness, Peripheral neuropathy, Toe and heel gait defect, Walking difficultiesTFP210Intron 4
HADHB_0017c.248C>Gp.Ala83GlyNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB<3354037301Muscle weaknessTFP248Exon 5
HADHB_0018c.254+1G>AIntronicNot SpecifiedPathogenic03/01/2023SNVSplice donorHADHB<324379101, 286414772Arrhythmia, Elevated circulating creatine kinase concentration, Fever, Herpetic gingivostomatitis, Hypotonia, Lethargy, Malaise/fatigue, Muscle weakness, Poor feeding, RhabdomyolysisTFP254Intron 5
HADHB_0019c.254+5G>AIntronicNot SpecifiedUncertain Significance03/01/2023SNVSplice regionHADHB<3353839651Abnormality of metabolism/homeostasis, Cardiomyopathy, HypoglycemiaTFP254Intron 5
HADHB_0020c.255-713_811+86delp.Gly86Lysfs*8Not SpecifiedUncertain Significance03/01/2023Copy Number LossHADHB<3322572951Cardiomyopathy, Elevated circulating creatine kinase concentration, Elevated hepatic transaminase, Weak motor skillsTFP255Exon 6-9, Intron 5-9
HADHB_0021c.255-1G>AIntronicNot SpecifiedPathogenic03/01/2023SNVSplice acceptorHADHB<333123633, 354331692Decreased body weight, Decreased enduranceTFP255Intron 5
HADHB_0022c.340A>Gp.Asn114AspNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB3-517143551, 295192412Abnormality of metabolism/homeostasis, Difficulty climbing stairs, Difficulty running, Elevated hepatic transaminase, Lethargy, Peripheral neuropathy, Positive gowers sign, Rhabdomyolysis, Urine discolorationTFP340Exon 6
HADHB_0023c.341A>Gp.Asn114SerNot SpecifiedPathogenic03/01/2023SNVMissenseHADHB3-515902556, 17431731, 261092583TFP341Exon 6
HADHB_0024c.349A>Gp.Arg117GlyNot SpecifiedPathogenic03/01/2023SNVMissenseHADHB<3127547061Myopathy, Peripheral neuropathyTFP349Exon 6
HADHB_0025c.354+5delIntronicNot SpecifiedUncertain Significance03/01/2023DeletionSplice regionHADHB<3353839651Abnormality of metabolism/homeostasis, Cardiac-other, Cardiomyopathy, Hypoglycemia, Pulmonary/respiratoryTFP354Intron 6
HADHB_0026c.357dupp.Ala120Cysfs*8Not SpecifiedPathogenic03/01/2023DuplicationFrameshiftHADHB<3198807691Abnormality of metabolism/homeostasis, Cardiac-other, Cardiomyopathy, Chest retractions with grunting sounds, Decreased activity, Hypotension, Liquefaction of hemorrhages, Pale appearance, Pulmonary/respiratory, Renal insufficiency/failure, SeizureTFP357Exon 7
HADHB_0027c.362T>Cp.Leu121ProNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<3127547061TFP362Exon 7
HADHB_0028c.392C>Tp.Ala131ValNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<3323488391Elevated circulating creatine kinase concentration, Mitochondrial myopathy, Recurrent attacksTFP392Exon 7
HADHB_0029c.397A>Gp.Thr133AlaNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB6-1035383965, 354037302Abnormal gait, Exercise intolerance, Hypotonia, Loss of balance, Muscle weakness, Myalgia, RhabdomyolysisTFP397Exon 7
HADHB_0030c.397A>Cp.Thr133ProNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB<3127547061Hellp syndrome, MyopathyTFP397Exon 7
HADHB_0031c.407T>Cp.Met136ThrNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB3-531521624, 323488392Diminished tendon reflex, Elevated circulating creatine kinase concentration, Exercise intolerance, Malaise/fatigue, Mitochondrial myopathy, Muscle weakness, Myalgia, Myoglobinuria, Recurrent attacks, Rhabdomyolysis, Urine discolorationTFP407Exon 7
HADHB_0032c.421G>Ap.Ala141ThrNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<3315216241Diminished tendon reflex, Elevated circulating creatine kinase concentration, Exercise intolerance, Malaise/fatigue, Muscle weakness, Myalgia, Myoglobinuria, Rhabdomyolysis, Urine discolorationTFP421Exon 7
HADHB_0033c.426C>Ap.Asn142LysNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<311196108, 159025562TFP426Exon 7
HADHB_0034c.427C>Gp.Gln143GluNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<3323488391Elevated circulating creatine kinase concentration, Mitochondrial myopathy, Recurrent attacksTFP427Exon 7
HADHB_0035c.442+614A>GIntronicNot SpecifiedLikely Pathogenic03/01/2023SNVIntronicHADHB3-515056246, 18693053, 270145693Abnormality of metabolism/homeostasis, Anuria, Cardiac-other, Cyanosis, Elevated circulating creatine kinase concentration, Hyperammonemia, Hypoketotic hypoglycemia, Intraventricular and pulmonary hemorrhage, Pulmonary/respiratory, Renal insufficiency/failure, Seizure, VomitingTFP442Intron 7
HADHB_0036c.442+663A>GIntronicNot SpecifiedUncertain Significance03/01/2023SNVIntronicHADHB<3300296941Abnormality of metabolism/homeostasis, Cardiac-other, Dilated cardiomyopathyTFP442Intron 7
HADHB_0037c.443-20_624delinsCACACAAGIntronicNot SpecifiedUncertain Significance03/01/2023DelinsHADHB<3315759111Abnormality of metabolism/homeostasisTFP443Exon 8, Intron 7
HADHB_0038c.443-10T>CIntronicNot SpecifiedUncertain Significance05/16/2023SNVIntronicHADHB<30TFP443Intron 7
HADHB_0039c.490G>Ap.Gly164SerNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<3347121951Distal muscle weakness, RhabdomyolysisTFP490Exon 8
HADHB_0040c.520C>Tp.Arg174CysIntramembranePathogenic03/01/2023SNVMissenseHADHB3-522000755, 28515471, 323488393Apparent life-threatening event, Difficulty in moving, Elevated circulating creatine kinase concentration, Elevated circulating myoglobin concentration, Malaise/fatigue, Mitochondrial myopathy, Myalgia, Peripheral neuropathy, Recurrent attacks, RhabdomyolysisTFP520Exon 8
HADHB_0041c.522dupp.His175Serfs*11IntramembranePathogenic03/01/2023DuplicationFrameshiftHADHB<311196108, 159025562Abnormality of metabolism/homeostasis, Abnormality of the liver, Encephalopathy, Hypotension, Lethargy, Neutropenia, Pulmonary/respiratory, VomitingTFP522Exon 8
HADHB_0042c.527C>Gp.Ser176*IntramembranePathogenic03/01/2023SNVNonsenseHADHB<3127547061TFP527Exon 8
HADHB_0043c.565G>Ap.Ala189ThrIntramembraneUncertain Significance05/16/2023SNVMissenseHADHB<30TFP565Exon 8
HADHB_0044c.574A>Gp.Met192ValIntramembraneUncertain Significance05/16/2023SNVMissenseHADHB<30TFP574Exon 8
HADHB_0045c.580C>Tp.Gln194*IntramembranePathogenic03/01/2023SNVNonsenseHADHB<330682426, 336382022TFP580Exon 8
HADHB_0046c.584G>Ap.Arg195GlnIntramembraneUncertain Significance05/16/2023SNVMissenseHADHB<30TFP584Exon 8
HADHB_0047c.607C>Tp.Arg203*IntramembranePathogenic03/01/2023SNVNonsenseHADHB<3127547061Myopathy, Peripheral neuropathyTFP607Exon 8
HADHB_0048c.631-1G>AIntronicNot SpecifiedPathogenic03/01/2023SNVSplice acceptorHADHB<330682426, 353839652Abnormality of metabolism/homeostasis, CardiomyopathyTFP631Intron 8
HADHB_0049c.640G>Ap.Val214IleIntramembraneUncertain Significance05/16/2023SNVMissenseHADHB<30TFP640Exon 9
HADHB_0050c.646G>Tp.Glu216*IntramembranePathogenic05/16/2023SNVNonsenseHADHB<30TFP646Exon 9
HADHB_0051c.685C>Tp.Arg229*Not SpecifiedPathogenic03/01/2023SNVNonsenseHADHB<3127547061TFP685Exon 9
HADHB_0052c.686G>Ap.Arg229GlnNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB3-530990523, 347121952Bulb atrophy, Distal muscle weakness, Malaise/fatigue, Muscle weakness, Myopathy, Neovascular glaucoma, Pain, Peripheral neuropathy, RhabdomyolysisTFP686Exon 9
HADHB_0053c.686G>Tp.Arg229LeuNot SpecifiedPathogenic03/01/2023SNVMissenseHADHB3-5243140341Abnormal motor nerve conduction velocities, Absent deep tendon reflexes, Atrophy, Atrophy of bilateral distal muscles, Bilateral foot drop, Distal muscle weakness, Disturbed vibration and position senses, Gait disability, Gait disturbance, Loss of sensory and tendon reflexes, Lower limb muscle weakness, Muscle weakness, Peripheral neuropathy, Toe and heel gait defect, Walking difficultiesTFP686Exon 9
HADHB_0054c.693delp.Ala232Leufs*20Not SpecifiedPathogenic03/01/2023DeletionFrameshiftHADHB<3127547061HypoglycemiaTFP693Exon 9
HADHB_0055c.694G>Ap.Ala232ThrNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB6-1035403730, 354331692Developmental delay, Muscle weaknessTFP694Exon 9
HADHB_0056c.712C>Tp.Arg238TrpNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<3306824261Abnormal fibre size variations, Abnormal renal morphology, Areflexia, Distal muscular atrophy, Elevated circulating creatine kinase concentration, Muscle weakness, Peripheral neuropathy, Rhabdomyolysis, Sensorimotor deficits, Small statureTFP712Exon 9
HADHB_0057c.713G>Ap.Arg238GlnNot SpecifiedUncertain Significance05/16/2023SNVMissenseHADHB<30TFP713Exon 9
HADHB_0058c.725A>Gp.Asp242GlyNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB<3127547061HypoglycemiaTFP725Exon 9
HADHB_0059c.739C>Tp.Arg247CysNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB6-1019699128, 22841441, 28649548, 29519241, 299150905Abnormality of metabolism/homeostasis, Arrhythmia, Coma, Decreased liver function, Developmental delay, Difficulty climbing stairs, Difficulty running, Dragging gait, Elevated circulating creatine kinase concentration, Exercise intolerance, Fever, High-arched feet, Lethargy, Loss of achilles tendon reflex, Loss of knee jerk reflex, Lower limb muscle weakness, Myalgia, Peripheral neuropathy, Reduced lower extremity muscle volume, Rhabdomyolysis, Seizure, Trouble climbing stairsTFP739Exon 9
HADHB_0060c.740G>Ap.Arg247HisNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB3-512754706, 15617873, 865128233-hydroxydicarboxylic aciduria, Cardiomyopathy, Decreased body weight, Decreased liver function, Hyperammonemia, Hypoglycemia, Intestinal pseudo-obstruction, Muscle weakness, Myopathy, Peripheral neuropathy, Rhabdomyolysis, VomitingTFP740Exon 9
HADHB_0061c.776_777insTp.Leu260Thrfs*4Not SpecifiedPathogenic03/01/2023InsertionFrameshiftHADHB<319699128, 28515471, 8645256, 92592664Abnormality of metabolism/homeostasis, Cardiac arrest, Cardiomyopathy, Decreased liver function, Developmental delay, Elevated circulating creatine kinase concentration, Encephalopathy, Hypoparathyroidism, Hypotonia, Lethargy, Pulmonary/respiratoryTFP776Exon 9
HADHB_0062c.788A>Gp.Asp263GlyNot SpecifiedPathogenic03/01/2023SNVMissenseHADHB3-521549624, 28392417, 8163672, 86512824Hypoglycemia, RhabdomyolysisTFP788Exon 9
HADHB_0063c.811+82A>GIntronicNot SpecifiedUncertain Significance03/01/2023SNVIntronicHADHB<3322572951Cardiomyopathy, Elevated circulating creatine kinase concentration, Elevated hepatic transaminase, Weak motor skillsTFP811Intron 9
HADHB_0064c.817delp.Asp273Ilefs*20Not SpecifiedPathogenic03/01/2023DeletionFrameshiftHADHB<319699128, 228414412Abnormality of metabolism/homeostasis, Coma, Decreased liver function, Developmental delay, SeizureTFP817Exon 10
HADHB_0065c.839G>Ap.Gly280AspNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<3127547061HypoglycemiaTFP839Exon 10
HADHB_0066c.845G>Ap.Arg282HisNot SpecifiedUncertain Significance05/16/2023SNVMissenseHADHB<30TFP845Exon 10
HADHB_0067c.881C>Tp.Pro294LeuNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB<3127547061Myopathy, Peripheral neuropathyTFP881Exon 10
HADHB_0068c.881C>Gp.Pro294ArgNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB<3127547061Hellp syndrome, Hypoglycemia, MyopathyTFP881Exon 10
HADHB_0069c.901G>Ap.Gly301SerNot SpecifiedUncertain Significance05/16/2023SNVMissenseHADHB6-1012754706, 12809642, 16040264, 16996288, 20589231, 274913976TFP901Exon 10
HADHB_0070c.902G>Ap.Gly301AspNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB<311196108, 159025562TFP902Exon 10
HADHB_0071c.919A>Gp.Asn307AspNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB3-517143551, 295192412Abnormality of metabolism/homeostasis, Difficulty running, Elevated hepatic transaminase, Lethargy, Myoglobinuria, Pericardial effusion, Peripheral neuropathy, Positive gowers sign, Renal insufficiency/failure, Respiratory tract infection, Rhabdomyolysis, Urine discoloration, Walk with assistanceTFP919Exon 10
HADHB_0072c.965C>Ap.Ala322GluNot SpecifiedUncertain Significance05/16/2023SNVMissenseHADHB<30TFP965Exon 11
HADHB_0073c.976G>Cp.Ala326ProNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB6-10125483841Abnormality of metabolism/homeostasis, Bilateral hydrothoraces, Cardiac-other, Elevated circulating creatine kinase concentration, Hydrops generalisatus, Hypotonia, Myopathy, Pulmonary/respiratoryTFP976Exon 11
HADHB_0074c.980T>Cp.Leu327ProNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<3286854931Abnormality of metabolism/homeostasis, Areflexia, Arrhythmia, Diarrhea, Difficulty moving arms, Difficulty speaking, Difficulty swallowing, Dyspnoea, Elevated circulating creatine kinase concentration, Fever, Hypoesthesia, Hypoparathyroidism, Muscle spasm, Muscle weakness, Myalgia, Pain, Peripheral neuropathy, Pes cavus, Rhabdomyolysis, Sensory deficits, Shuddering attacks, Upper quadrant abdominal tenderness, Urine discoloration, VomitingTFP980Exon 11
HADHB_0075c.998C>Tp.Pro333LeuNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<3354331691Decreased body weight, Decreased enduranceTFP998Exon 11
HADHB_0076c.1000A>Cp.Lys334GlnNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB30+0TFP1000Exon 11
HADHB_0077c.1059delp.Gly354Aspfs*10Not SpecifiedPathogenic03/01/2023DeletionFrameshiftHADHB3-526334177, 27995076, 286174193TFP1059Exon 12
HADHB_0078c.1091A>Gp.Glu364GlyNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<3345788031TFP1091Exon 13
HADHB_0079c.1115A>Tp.Asp372ValNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB<3336382021TFP1115Exon 13
HADHB_0080c.1136A>Gp.His379ArgNot SpecifiedPathogenic03/01/2023SNVMissenseHADHB6-1015056246, 18693053, 25420603, 295192414Abnormality of metabolism/homeostasis, Anuria, Cardiac-other, Cardiomyopathy, Cyanosis, Elevated circulating creatine kinase concentration, Hyperammonemia, Hypoketotic hypoglycemia, Intraventricular and pulmonary hemorrhage, Pulmonary/respiratory, Renal insufficiency/failure, Seizure, VomitingTFP1136Exon 13
HADHB_0081c.1137delp.His379Glnfs*76Not SpecifiedPathogenic03/01/2023DeletionFrameshiftHADHB<3215496241TFP1137Exon 13
HADHB_0082c.1148C>Tp.Ser383LeuNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB<3295192411Difficulty running, Peripheral neuropathy, RhabdomyolysisTFP1148Exon 13
HADHB_0083c.1149+4A>GIntronicNot SpecifiedUncertain Significance05/16/2023SNVSplice regionHADHB<30TFP1149Intron 13
HADHB_0084c.1154A>Cp.Gln385ProNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB3-5281125271Asphyxiation, Cardiomyopathy, Decreased liver function, Hypoketotic hypoglycemiaTFP1154Exon 14
HADHB_0085c.1165A>Gp.Asn389AspNot SpecifiedPathogenic03/01/2023SNVMissenseHADHB6-1017143551, 21549624, 28392417, 29519241, 299150905Myoglobinuria, Myopathy, Pericardial effusion, Peripheral neuropathy, Renal insufficiency/failure, Respiratory tract infection, Rhabdomyolysis, Walk with assistanceTFP1165Exon 14
HADHB_0086c.1175C>Tp.Ala392ValNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB6-1024664533, 28515471, 325095333Abnormality of metabolism/homeostasis, Absence of achilles and patellar tendon reflexes, Atrophy, Cardiac arrest, Difficulty walking, Diminished touch senses, Drop foot, Elevated circulating creatine kinase concentration, Fever, Hammer toes, Hypoglycemia, Hypoparathyroidism, Muscle weakness, Myoglobinuria, Peripheral neuropathy, Pulmonary/respiratory, Rhabdomyolysis, SeizureTFP1175Exon 14
HADHB_0087c.1175_1177delp.Ala392_Met393delinsValNot SpecifiedUncertain Significance03/01/2023DeletionDeletionHADHB<3215496241TFP1175Exon 14
HADHB_0088c.1191G>Ap.Trp397*Not SpecifiedPathogenic03/01/2023SNVNonsenseHADHB<3215496241TFP1191Exon 14
HADHB_0089c.1192T>Cp.Phe398LeuNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<3281329771Malaise/fatigue, Muscle weakness, Peripheral neuropathy, Rhabdomyolysis, Sensory disturbances, Urine discolorationTFP1192Exon 14
HADHB_0090c.1198G>Tp.Glu400*Not SpecifiedPathogenic03/01/2023SNVNonsenseHADHB<3300296941Abnormality of metabolism/homeostasis, Cardiac-other, Dilated cardiomyopathyTFP1198Exon 14
HADHB_0091c.1211dupp.Arg405*Not SpecifiedPathogenic03/01/2023DuplicationFrameshiftHADHB<3295192411Abnormality of metabolism/homeostasis, Cardiomyopathy, Pulmonary/respiratoryTFP1211Exon 14
HADHB_0092c.1228_1240delp.Gly410Trpfs*41Not SpecifiedPathogenic03/01/2023DeletionFrameshiftHADHB<3315276761Dilated cardiomyopathyTFP1228Exon 15
HADHB_0093c.1279G>Ap.Gly427ArgNot SpecifiedUncertain Significance05/16/2023SNVMissenseHADHB<30TFP1279Exon 15
HADHB_0094c.1280G>Ap.Gly427GluNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<3301937511TFP1280Exon 15
HADHB_0095c.1289T>Cp.Phe430SerNot SpecifiedLikely Pathogenic05/16/2023SNVMissenseHADHB3-516423905, 35383965, 35403730, 357826144Abnormality of metabolism/homeostasis, Cardiac-other, Cardiomyopathy, Feeding difficulties, Hyaline membrane disease of the lungs, Hypoglycemia, Hypotonia, Myalgia, Pulmonary/respiratory, Respiratory tract infection, RhabdomyolysisTFP1289Exon 15
HADHB_0096c.1331G>Ap.Arg444LysNot SpecifiedLikely Pathogenic03/01/2023SNVMissenseHADHB11-2011239956, 19699128, 22000755, 26109258, 28515471, 8645256, 9259266, 93053498Abnormality of metabolism/homeostasis, Apparent life-threatening event, Cardiac arrest, Cardiomyopathy, Decreased liver function, Developmental delay, Difficulty in moving, Difficulty in walking, Diminished muscle stretch reflexes, Elevated circulating creatine kinase concentration, Elevated circulating myoglobin concentration, Encephalopathy, Hypoparathyroidism, Hypotonia, Lethargy, Malaise/fatigue, Muscle weakness, Myalgia, Myoglobinuria, Nausea, Peripheral neuropathy, Pigmenturia, Pulmonary/respiratory, Rhabdomyolysis, Urine discolorationTFP1331Exon 15
HADHB_0097c.1336C>Tp.Arg446TrpNot SpecifiedUncertain Significance05/16/2023SNVMissenseHADHB<30TFP1336Exon 15
HADHB_0098c.1348G>Tp.Gly450CysNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<3345788031TFP1348Exon 15
HADHB_0099c.1364T>Gp.Val455GlyNot SpecifiedPathogenic03/01/2023SNVMissenseHADHB6-1019699128, 19880769, 27014569, 28515471, 325095335Abnormality of metabolism/homeostasis, Cardiac arrest, Cardiac-other, Cardiomyopathy, Chest retractions with grunting sounds, Cyanosis, Decreased activity, Decreased liver function, Elevated circulating creatine kinase concentration, Hyperammonemia, Hypoglycemia, Hypoparathyroidism, Hypotension, Liquefaction of hemorrhages, Pale appearance, Pulmonary/respiratory, Renal insufficiency/failure, Rhabdomyolysis, SeizureTFP1364Exon 15
HADHB_0100c.1376C>Ap.Ala459GluNot SpecifiedUncertain Significance03/01/2023SNVMissenseHADHB<311196108, 159025562Abnormality of metabolism/homeostasis, Abnormality of the liver, Encephalopathy, Hypotension, Lethargy, Neutropenia, Pulmonary/respiratory, VomitingTFP1376Exon 15
HADHB_0101c.1390-515_1390-499delIntronicNot SpecifiedLikely Pathogenic03/01/2023DeletionIntronicHADHB<3282835301TFP1390Intron 15
HADHB_0102c.1409A>Cp.Glu470AlaNot SpecifiedUncertain Significance05/16/2023SNVMissenseHADHB<30TFP1409Exon 16
    Notes:
  • * All variants are referencing NM_000183.2 and NM_000183.3 and there is no change between these versions with respect to the coding sequence.
  • * Genomic coordinates are calculated based on variant data provided: in some cases coordinates are estimated in order to allow users to sort the variants linearly, by approximation.
    Definition of acronyms:
  • "*": Referenced a stop codon insertion when listed under amino acid change.
  • ACMG: American College of Medical Genetics and Genomics
  • CNV: Copy number variant which here describes a change 100 DNA nucleotides or larger.
  • SNV: Single DNA nucleotide variant
  • del: Deletion
  • dup: Duplication
  • fs: Frameshift
  • ins: Insertion

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