Total 64 pathogenic variants reported for Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis

Variant Name	Variant Type	Variant Genomic Location	Clinical Significance	Phenotype Condition	Review Status	ClinGen Allele	dbSNP ID	Variation/condition record
NM_021830.5(TWNK):c.1422G>A (p.Trp474Ter)	SNV Germline	Chr10:100989822	Likely pathogenic	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Infantile onset spinocerebellar ataxia Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Perrault syndrome 5	Criteria Provided Single Submitter	CA116960	rs_111033574	2 SubmittersRCV000004882 RCV002496262
NM_021830.5(TWNK):c.955A>G (p.Lys319Glu)	SNV Germline	Chr10:100989165	Pathogenic	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis	No Assertion Criteria Provided	CA116968	rs_80356543	2 SubmittersRCV000004888 RCV000020867
NM_002693.3(POLG):c.1399G>A (p.Ala467Thr)	SNV Germline	Chr15:89327201	Pathogenic	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Spinocerebellar ataxia with epilepsy Progressive sclerosing poliodystrophy Condition: not provided Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 POLG-Related Spectrum Disorders 6 conditions Mitochondrial disease Mitochondrial DNA depletion syndrome 4b Progressive sclerosing poliodystrophy POLG-related disorder Mitochondrial DNA depletion syndrome 4b Tip-toe gait Mitochondrial DNA depletion syndrome 4b Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Progressive sclerosing poliodystrophy Mitochondrial DNA depletion syndrome 4b Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Progressive sclerosing poliodystrophy Inborn genetic diseases Hereditary spastic paraplegia Neurodevelopmental delay	Criteria Provided Multiple Submitters No Conflicts	CA123140	rs_113994095	44 SubmittersRCV000014440 RCV000014441 RCV000014442 RCV000014443 RCV000188658 RCV000184011 RCV000347876 RCV000515354 RCV000508942 RCV001004604 RCV001095683 RCV001198082 RCV001376079 RCV001731286 RCV001813983 RCV002316195 RCV001847600 RCV002273931
NM_002693.3(POLG):c.1879C>T (p.Arg627Trp)	SNV Germline	Chr15:89325520	Pathogenic	Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive sclerosing poliodystrophy Condition: not provided Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections Primary familial dilated cardiomyopathy Mitochondrial DNA depletion syndrome	Criteria Provided Multiple Submitters No Conflicts	CA256887	rs_121918046	5 SubmittersRCV000014446 RCV001382679 RCV001781264 RCV004525852 RCV004541004 RCV004579531
NM_002693.3(POLG):c.2794C>T (p.His932Tyr)	SNV Germline	Chr15:89320953	Pathogenic	Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive sclerosing poliodystrophy Condition: not provided	Criteria Provided Multiple Submitters No Conflicts	CA256891	rs_121918048	4 SubmittersRCV000014454 RCV000758263 RCV001797046
NM_002693.3(POLG):c.3151G>C (p.Gly1051Arg)	SNV Germline	Chr15:89319053	Conflicting classifications of pathogenicity	Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Condition: not provided Progressive sclerosing poliodystrophy POLG-Related Spectrum Disorders Intellectual disability See cases	Criteria Provided Conflicting Classifications	CA256893	rs_121918049	10 SubmittersRCV000014455 RCV000188604 RCV000226986 RCV000778451 RCV001252354 RCV002251905
NM_002693.3(POLG):c.2542G>A (p.Gly848Ser)	SNV Germline	Chr15:89321792	Pathogenic	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Progressive external ophthalmoplegia with mitochondrial DNA deletions, digenic Progressive sclerosing poliodystrophy Mitochondrial DNA depletion syndrome 4b Condition: not provided POLG-Related Spectrum Disorders 6 conditions Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Mitochondrial DNA depletion syndrome 4b Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Progressive sclerosing poliodystrophy Mitochondrial disease Inborn genetic diseases Mitochondrial DNA depletion syndrome 4b Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Progressive sclerosing poliodystrophy Hereditary spastic paraplegia POLG-related disorder Mitochondrial DNA depletion syndrome	Criteria Provided Multiple Submitters No Conflicts	CA123144	rs_113994098	35 SubmittersRCV000014449 RCV000014450 RCV000014451 RCV000014452 RCV000188580 RCV000363602 RCV000515163 RCV000678386 RCV001027839 RCV002272018 RCV002313707 RCV002054437 RCV001847601 RCV003231103 RCV003230362
NM_002693.3(POLG):c.752C>T (p.Thr251Ile)	SNV Germline	Chr15:89330184	Conflicting classifications of pathogenicity	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Mitochondrial DNA depletion syndrome 4b Mitochondrial DNA depletion syndrome 1 Progressive sclerosing poliodystrophy Condition: not provided not specified POLG-Related Spectrum Disorders Global developmental delay Mitochondrial DNA depletion syndrome 4b Progressive sclerosing poliodystrophy Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Tip-toe gait Hereditary spastic paraplegia POLG-related disorder Abnormality of the nervous system Inborn genetic diseases Mitochondrial disease Hypertrophic cardiomyopathy Mitochondrial DNA depletion syndrome 4b Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Progressive sclerosing poliodystrophy See cases	Criteria Provided Conflicting Classifications	CA123142	rs_11394094	44 SubmittersRCV000014447 RCV000014448 RCV000020484 RCV000184009 RCV000188641 RCV000194055 RCV000262479 RCV000415105 RCV001004407 RCV001642225 RCV001678594 RCV001847602 RCV001813742 RCV001813985 RCV002313708 RCV002272019 RCV002319423 RCV003458331 RCV004584325
NM_002693.3(POLG):c.1760C>T (p.Pro587Leu)	SNV Germline	Chr15:89325639	Conflicting classifications of pathogenicity	Mitochondrial DNA depletion syndrome 4b Mitochondrial DNA depletion syndrome 1 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 not specified Global developmental delay Progressive sclerosing poliodystrophy Condition: not provided Mitochondrial disease Mitochondrial DNA depletion syndrome 4b Progressive sclerosing poliodystrophy Tip-toe gait Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis POLG-related disorder Abnormality of the nervous system Hypertrophic cardiomyopathy Hereditary spastic paraplegia Inborn genetic diseases Mitochondrial DNA depletion syndrome 4b Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Progressive sclerosing poliodystrophy See cases	Criteria Provided Conflicting Classifications	CA123146	rs_113994096	47 SubmittersRCV000014456 RCV000020473 RCV000186576 RCV000193529 RCV000415307 RCV000408293 RCV000427845 RCV000508752 RCV001004602 RCV001610290 RCV001642226 RCV001813743 RCV001813986 RCV002319424 RCV001847603 RCV002313709 RCV003458332 RCV004584326
NM_002693.3(POLG):c.2243G>C (p.Trp748Ser)	SNV Germline	Chr15:89323426	Pathogenic/Likely pathogenic	Progressive sclerosing poliodystrophy Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Spinocerebellar ataxia with epilepsy Condition: not provided POLG-Related Spectrum Disorders Mitochondrial disease not specified Mitochondrial DNA depletion syndrome 4b Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Inborn genetic diseases POLG-related disorder	Criteria Provided Multiple Submitters No Conflicts	CA123150	rs_113994097	36 SubmittersRCV000014461 RCV000014459 RCV000014460 RCV000080023 RCV000313739 RCV000508846 RCV000507757 RCV001198081 RCV002247336 RCV002313710 RCV003985719
NM_002693.3(POLG):c.2209G>C (p.Gly737Arg)	SNV Germline	Chr15:89323460	Pathogenic/Likely pathogenic	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Condition: not provided Progressive sclerosing poliodystrophy POLG-Related Spectrum Disorders Mitochondrial disease Mitochondrial DNA depletion syndrome 4b Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Progressive sclerosing poliodystrophy Mitochondrial DNA depletion syndrome 4b Progressive sclerosing poliodystrophy Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Hereditary spastic paraplegia Inborn genetic diseases Tip-toe gait POLG-related disorder	Criteria Provided Multiple Submitters No Conflicts	CA201029	rs_121918054	30 SubmittersRCV000014467 RCV000188568 RCV000233045 RCV000370280 RCV000508744 RCV000768053 RCV001004601 RCV001813987 RCV001847605 RCV002316196 RCV003318542 RCV003985721
NM_198859.4(PRICKLE2):c.1813G>T (p.Val605Phe)	SNV Germline	Chr3:64099773	Conflicting classifications of pathogenicity	Progressive myoclonic epilepsy type 5 Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis not specified Condition: not provided	Criteria Provided Conflicting Classifications	CA129419	rs_387906989	4 SubmittersRCV000023710 RCV000679893 RCV002247388 RCV004555849
NM_002693.3(POLG):c.1550G>T (p.Gly517Val)	SNV Germline	Chr15:89326947	Conflicting classifications of pathogenicity	Mitochondrial disease Idiopathic camptocormia Condition: not provided Progressive sclerosing poliodystrophy not specified Tip-toe gait Inborn genetic diseases POLG-related disorder Progressive sclerosing poliodystrophy Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Mitochondrial DNA depletion syndrome 4b Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 POLG-Related Spectrum Disorders Hereditary spastic paraplegia	Criteria Provided Conflicting Classifications	CA204012	rs_61752783	24 SubmittersRCV000055881 RCV000186556 RCV000223970 RCV000229511 RCV000118011 RCV001352901 RCV002311532 RCV003985725 RCV000768289 RCV001117969 RCV001847644
NM_021830.5(TWNK):c.639C>T (p.Gly213=)	SNV Germline	Chr10:100988849	Conflicting classifications of pathogenicity	not specified Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Infantile onset spinocerebellar ataxia Autosomal recessive cerebellar ataxia Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Condition: not provided Hereditary spastic paraplegia	Criteria Provided Conflicting Classifications	CA302706	rs_11542130	8 SubmittersRCV000173516 RCV000359159 RCV000305599 RCV000395926 RCV000301625 RCV000676300 RCV001847741
NM_021830.5(TWNK):c.1735-14C>A	SNV Germline	Chr10:100993176	Conflicting classifications of pathogenicity	not specified Infantile onset spinocerebellar ataxia Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Autosomal recessive cerebellar ataxia Condition: not provided	Criteria Provided Conflicting Classifications	CA289762	rs_201795189	4 SubmittersRCV000124046 RCV000314586 RCV000335702 RCV000369307 RCV000396649 RCV002055436
NM_002693.3(POLG):c.2601T>C (p.Pro867=)	SNV Germline	Chr15:89321258	Conflicting classifications of pathogenicity	not specified POLG-Related Spectrum Disorders Progressive sclerosing poliodystrophy Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Mitochondrial DNA depletion syndrome 4b Condition: not provided Progressive sclerosing poliodystrophy POLG-related disorder	Criteria Provided Conflicting Classifications	CA292834	rs_201749977	6 SubmittersRCV000127526 RCV000403402 RCV000709782 RCV000734626 RCV001457683 RCV003985730
NM_002693.3(POLG):c.3482+6C>T	SNV Germline	Chr15:89318535	Conflicting classifications of pathogenicity	not specified POLG-Related Spectrum Disorders Progressive sclerosing poliodystrophy Condition: not provided Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Progressive sclerosing poliodystrophy Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Mitochondrial DNA depletion syndrome 4b Hereditary spastic paraplegia Mitochondrial DNA depletion syndrome 4b	Criteria Provided Conflicting Classifications	CA292847	rs_55779802	10 SubmittersRCV000127539 RCV000316461 RCV000559092 RCV000726414 RCV000768049 RCV001847754 RCV003441747
NM_021830.5(TWNK):c.1172G>A (p.Arg391His)	SNV Germline	Chr10:100989382	Conflicting classifications of pathogenicity	Perrault syndrome 5 Infantile onset spinocerebellar ataxia Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Autosomal recessive cerebellar ataxia Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Perrault syndrome Condition: not provided	Criteria Provided Conflicting Classifications	CA174962	rs_556445621	5 SubmittersRCV000149470 RCV000290037 RCV000305281 RCV000345001 RCV000403533 RCV002516006 RCV002516005
NM_002693.3(POLG):c.1837C>T (p.His613Tyr)	SNV Germline	Chr15:89325562	Conflicting classifications of pathogenicity	not specified Progressive sclerosing poliodystrophy Condition: not provided Progressive sclerosing poliodystrophy Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Mitochondrial DNA depletion syndrome 4b Global developmental delay Inborn genetic diseases POLG-related disorder	Criteria Provided Conflicting Classifications	CA302712	rs_147407423	14 SubmittersRCV000173762 RCV000538134 RCV000710183 RCV000768055 RCV001263354 RCV002313026 RCV003985737
NM_002693.3(POLG):c.803G>C (p.Gly268Ala)	SNV Germline	Chr15:89330133	Conflicting classifications of pathogenicity	not specified Progressive sclerosing poliodystrophy Condition: not provided POLG-related disorder Progressive sclerosing poliodystrophy Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Mitochondrial DNA depletion syndrome 4b POLG-Related Spectrum Disorders Hereditary spastic paraplegia Tip-toe gait Inborn genetic diseases Charcot-Marie-Tooth disease axonal type 2U	Criteria Provided Conflicting Classifications	CA202319	rs_61752784	20 SubmittersRCV000177165 RCV000233823 RCV000415771 RCV000709833 RCV000768291 RCV001121511 RCV001847817 RCV002227084 RCV002312719 RCV002516726
NM_002693.3(POLG):c.3139C>T (p.Arg1047Trp)	SNV Germline	Chr15:89319065	Conflicting classifications of pathogenicity	Condition: not provided Progressive sclerosing poliodystrophy Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Inborn genetic diseases Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive sclerosing poliodystrophy Spinocerebellar ataxia with epilepsy not specified	Criteria Provided Conflicting Classifications	CA316740	rs_181860632	15 SubmittersRCV000188603 RCV000633548 RCV001808470 RCV002247605 RCV002317146 RCV003483565 RCV003987434
NM_002693.3(POLG):c.2021G>A (p.Gly674Asp)	SNV Germline	Chr15:89324156	Conflicting classifications of pathogenicity	not specified Progressive sclerosing poliodystrophy Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Mitochondrial DNA depletion syndrome 4b Progressive sclerosing poliodystrophy POLG-Related Spectrum Disorders Condition: not provided Inborn genetic diseases POLG-related disorder	Criteria Provided Conflicting Classifications	CA316585	rs_200257554	9 SubmittersRCV000188510 RCV000633561 RCV000768054 RCV001121414 RCV001721213 RCV002317140 RCV003985742
NM_002693.3(POLG):c.1808T>C (p.Met603Thr)	SNV Germline	Chr15:89325591	Conflicting classifications of pathogenicity	Condition: not provided Progressive sclerosing poliodystrophy Progressive sclerosing poliodystrophy Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Mitochondrial DNA depletion syndrome 4b not specified Hereditary spastic paraplegia	Criteria Provided Conflicting Classifications	CA316846	rs_367610201	6 SubmittersRCV000188667 RCV001348402 RCV001814096 RCV003226244 RCV001847837
NM_002693.3(POLG):c.1402A>G (p.Asn468Asp)	SNV Germline	Chr15:89327198	Conflicting classifications of pathogenicity	Progressive sclerosing poliodystrophy Condition: not provided Lennox-Gastaut syndrome 6 conditions Mitochondrial DNA depletion syndrome 4b Progressive sclerosing poliodystrophy Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Mitochondrial DNA depletion syndrome 4b Progressive sclerosing poliodystrophy POLG-Related Spectrum Disorders Seizure Intellectual disability Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Hereditary spastic paraplegia Inborn genetic diseases not specified	Criteria Provided Conflicting Classifications	CA316834	rs_145843073	22 SubmittersRCV000470781 RCV000658725 RCV000678827 RCV000763995 RCV001004603 RCV001027840 RCV001117972 RCV001263305 RCV001330959 RCV001610504 RCV001847836 RCV002314743 RCV003230444
NM_002693.3(POLG):c.1156C>T (p.Arg386Cys)	SNV Germline	Chr15:89328699	Conflicting classifications of pathogenicity	Condition: not provided Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive sclerosing poliodystrophy Mitochondrial DNA depletion syndrome 4b Progressive sclerosing poliodystrophy POLG-Related Spectrum Disorders Mitochondrial DNA depletion syndrome 4b	Criteria Provided Conflicting Classifications	CA316821	rs_199759055	10 SubmittersRCV000188650 RCV000660573 RCV000758259 RCV000778454 RCV003989500
NM_002693.3(POLG):c.862C>T (p.Arg288Cys)	SNV Germline	Chr15:89329104	Conflicting classifications of pathogenicity	Condition: not provided Progressive sclerosing poliodystrophy Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Mitochondrial DNA depletion syndrome 4b Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive sclerosing poliodystrophy	Criteria Provided Conflicting Classifications	CA316815	rs_564582352	4 SubmittersRCV000188646 RCV000768290 RCV000806434
NM_002693.3(POLG):c.678G>C (p.Gln226His)	SNV Germline	Chr15:89330258	Conflicting classifications of pathogenicity	Progressive sclerosing poliodystrophy Autism Seizure Condition: not provided POLG-Related Spectrum Disorders Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Inborn genetic diseases not specified	Criteria Provided Conflicting Classifications	CA316806	rs_147282197	16 SubmittersRCV000633538 RCV000678826 RCV000710188 RCV001121513 RCV001263148 RCV001808471 RCV002362986 RCV003317141
NM_002693.3(POLG):c.428C>T (p.Ala143Val)	SNV Germline	Chr15:89333327	Conflicting classifications of pathogenicity	Progressive sclerosing poliodystrophy POLG-Related Spectrum Disorders Condition: not provided Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis	Criteria Provided Conflicting Classifications		rs_796052899	8 SubmittersRCV000758269 RCV000779176 RCV000995420 RCV002288792
NM_002693.3(POLG):c.328C>T (p.His110Tyr)	SNV Germline	Chr15:89333427	Conflicting classifications of pathogenicity	Progressive sclerosing poliodystrophy Condition: not provided Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Mitochondrial DNA depletion syndrome 4b Progressive sclerosing poliodystrophy not specified Inborn genetic diseases	Criteria Provided Conflicting Classifications	CA316877	rs_139599587	9 SubmittersRCV000461638 RCV000727081 RCV000768048 RCV001804925 RCV002317148
NM_021830.5(TWNK):c.1196A>G (p.Asn399Ser)	SNV Germline	Chr10:100989406	Conflicting classifications of pathogenicity	Infantile onset spinocerebellar ataxia Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Autosomal recessive cerebellar ataxia Condition: not provided Perrault syndrome	Criteria Provided Conflicting Classifications	CA324207	rs_863223921	5 SubmittersRCV000578276 RCV001105894 RCV001105893 RCV001105895 RCV001722090 RCV002515383
NM_021830.5(TWNK):c.1697A>G (p.Lys566Arg)	SNV Germline	Chr10:100990973	Conflicting classifications of pathogenicity	not specified Infantile onset spinocerebellar ataxia Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Autosomal recessive cerebellar ataxia Condition: not provided TWNK-related disorder	Criteria Provided Conflicting Classifications	CA323752	rs_116046810	4 SubmittersRCV000199218 RCV000300073 RCV000284653 RCV000339690 RCV000402465 RCV000909034 RCV004530166
NM_021830.5(TWNK):c.1975G>A (p.Ala659Thr)	SNV Germline	Chr10:100993430	Conflicting classifications of pathogenicity	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Autosomal recessive cerebellar ataxia Infantile onset spinocerebellar ataxia Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Condition: not provided Infantile onset spinocerebellar ataxia Perrault syndrome 5 Perrault syndrome 5	Criteria Provided Conflicting Classifications	CA324977	rs_370814108	5 SubmittersRCV000267823 RCV000322888 RCV000326494 RCV000381173 RCV000712523 RCV001838991 RCV004558440
NM_021830.5(TWNK):c.2045G>A (p.Arg682His)	SNV Germline	Chr10:100993500	Conflicting classifications of pathogenicity	Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Autosomal recessive cerebellar ataxia Infantile onset spinocerebellar ataxia Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Condition: not provided Hereditary spastic paraplegia TWNK-related disorder	Criteria Provided Conflicting Classifications	CA323951	rs_182559752	6 SubmittersRCV000283282 RCV000374204 RCV000377740 RCV000338208 RCV000871398 RCV001847877 RCV004530167
NM_021830.5(TWNK):c.241C>G (p.Leu81Val)	SNV Germline	Chr10:100988451	Conflicting classifications of pathogenicity	Condition: not provided Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Hereditary spastic paraplegia Infantile onset spinocerebellar ataxia Autosomal recessive cerebellar ataxia	Criteria Provided Conflicting Classifications	CA5653043	rs_145068570	6 SubmittersRCV000320273 RCV001107964 RCV001102728 RCV001848043 RCV001107963 RCV001107965
NM_002693.3(POLG):c.2419C>T (p.Arg807Cys)	SNV Germline	Chr15:89322749	Conflicting classifications of pathogenicity	Condition: not provided Progressive sclerosing poliodystrophy Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 neonatal seizures Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis	Criteria Provided Conflicting Classifications	CA7724495	rs_769827124	8 SubmittersRCV000261805 RCV000547242 RCV000626194 RCV000678828 RCV001263147
NM_021830.5(TWNK):c.384C>T (p.Ser128=)	SNV Germline	Chr10:100988594	Conflicting classifications of pathogenicity	Infantile onset spinocerebellar ataxia Condition: not provided Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Autosomal recessive cerebellar ataxia Hereditary spastic paraplegia	Criteria Provided Conflicting Classifications	CA5653057	rs_148234280	6 SubmittersRCV000294722 RCV000336672 RCV000347919 RCV000351895 RCV000386725 RCV001848047
NM_021830.5(TWNK):c.-650A>G	SNV Germline	Chr10:100987561	Conflicting classifications of pathogenicity	Infantile onset spinocerebellar ataxia Autosomal recessive cerebellar ataxia Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Condition: not provided	Criteria Provided Conflicting Classifications	CA10627852	rs_187213541	2 SubmittersRCV000278960 RCV000336415 RCV000351651 RCV000403866 RCV002292507
NM_021830.5(TWNK):c.1042G>A (p.Gly348Arg)	SNV Germline	Chr10:100989252	Conflicting classifications of pathogenicity	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Autosomal recessive cerebellar ataxia Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Infantile onset spinocerebellar ataxia Condition: not provided Inborn genetic diseases	Criteria Provided Conflicting Classifications	CA5653154	rs_62626271	8 SubmittersRCV000273839 RCV000296339 RCV000331424 RCV000388304 RCV000994494 RCV004021460
NM_021830.5(TWNK):c.1488T>C (p.Thr496=)	SNV Germline	Chr10:100990439	Conflicting classifications of pathogenicity	Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Infantile onset spinocerebellar ataxia Autosomal recessive cerebellar ataxia Condition: not provided TWNK-related disorder	Criteria Provided Conflicting Classifications	CA5653252	rs_549767223	3 SubmittersRCV000301666 RCV000356457 RCV000359896 RCV000395193 RCV003105861 RCV004544498
NM_021830.5(TWNK):c.-290G>C	SNV Germline	Chr10:100987921	Conflicting classifications of pathogenicity	Infantile onset spinocerebellar ataxia Autosomal recessive cerebellar ataxia Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3	Criteria Provided Conflicting Classifications	CA10630756	rs_62626270	1 SubmittersRCV000260000 RCV000317524 RCV000374562 RCV000370858
NM_021830.5(TWNK):c.*301C>T	SNV Germline	Chr10:100993811	Conflicting classifications of pathogenicity	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Autosomal recessive cerebellar ataxia Infantile onset spinocerebellar ataxia	Criteria Provided Conflicting Classifications	CA10630757	rs_41291468	1 SubmittersRCV000261655 RCV000316885 RCV000320279 RCV000356361
NM_021830.5(TWNK):c.76G>A (p.Gly26Ser)	SNV Germline	Chr10:100988286	Conflicting classifications of pathogenicity	Autosomal recessive cerebellar ataxia Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Infantile onset spinocerebellar ataxia Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Condition: not provided	Criteria Provided Conflicting Classifications	CA5653019	rs_577209883	3 SubmittersRCV000311980 RCV000350458 RCV000398995 RCV000406517 RCV001515622
NM_021830.5(TWNK):c.492C>T (p.Leu164=)	SNV Germline	Chr10:100988702	Conflicting classifications of pathogenicity	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Infantile onset spinocerebellar ataxia Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Autosomal recessive cerebellar ataxia Condition: not provided	Criteria Provided Conflicting Classifications	CA5653070	rs_775463083	3 SubmittersRCV000279300 RCV000336716 RCV000395922 RCV000405350 RCV002262948
NM_021830.5(TWNK):c.922T>C (p.Leu308=)	SNV Germline	Chr10:100989132	Conflicting classifications of pathogenicity	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Autosomal recessive cerebellar ataxia Infantile onset spinocerebellar ataxia Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Condition: not provided	Criteria Provided Conflicting Classifications	CA5653139	rs_754389465	2 SubmittersRCV000270402 RCV000327796 RCV000366062 RCV000362650 RCV000872826
NM_021830.5(TWNK):c.1101C>T (p.Ile367=)	SNV Germline	Chr10:100989311	Conflicting classifications of pathogenicity	Autosomal recessive cerebellar ataxia Infantile onset spinocerebellar ataxia Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Hereditary spastic paraplegia Condition: not provided	Criteria Provided Conflicting Classifications	CA5653164	rs_200798080	3 SubmittersRCV000281131 RCV000316283 RCV000338588 RCV000373330 RCV001848070 RCV002059511
NM_021830.5(TWNK):c.*204G>A	SNV Germline	Chr10:100993714	Conflicting classifications of pathogenicity	Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Infantile onset spinocerebellar ataxia Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Autosomal recessive cerebellar ataxia Condition: not provided Hereditary spastic paraplegia	Criteria Provided Conflicting Classifications	CA10634372	rs_61871507	3 SubmittersRCV000308919 RCV000348968 RCV000363555 RCV000404345 RCV001582924 RCV001848071
NM_021830.5(TWNK):c.*419A>T	SNV Germline	Chr10:100993929	Conflicting classifications of pathogenicity	Infantile onset spinocerebellar ataxia Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Autosomal recessive cerebellar ataxia	Criteria Provided Conflicting Classifications	CA10634375	rs_187553791	1 SubmittersRCV000289702 RCV000293240 RCV000348190 RCV000390735
NM_021830.5(TWNK):c.1609T>C (p.Tyr537His)	SNV Germline	Chr10:100990885	Conflicting classifications of pathogenicity	Condition: not provided Infantile onset spinocerebellar ataxia Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Autosomal recessive cerebellar ataxia Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Hereditary spastic paraplegia not specified TWNK-related disorder	Criteria Provided Conflicting Classifications	CA5653294	rs_144001072	7 SubmittersRCV000726623 RCV001106000 RCV001105997 RCV001105998 RCV001105999 RCV001848766 RCV003993959 RCV004533016
NM_002693.3(POLG):c.1789C>T (p.Arg597Trp)	SNV Germline	Chr15:89325610	Pathogenic	Condition: not provided Progressive sclerosing poliodystrophy Inborn genetic diseases Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis	Criteria Provided Multiple Submitters No Conflicts	CA7724686	rs_139717885	7 SubmittersRCV000438492 RCV000758261 RCV004022346 RCV003147454
NM_021830.5(TWNK):c.56G>A (p.Gly19Glu)	SNV Germline	Chr10:100988266	Conflicting classifications of pathogenicity	Condition: not provided Infantile onset spinocerebellar ataxia Autosomal recessive cerebellar ataxia Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis	Criteria Provided Conflicting Classifications	CA5653011	rs_767175342	3 SubmittersRCV000489778 RCV001107307 RCV001107308 RCV001107309 RCV001107306
NM_021830.5(TWNK):c.1244-14C>T	SNV Germline	Chr10:100989630	Conflicting classifications of pathogenicity	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Infantile onset spinocerebellar ataxia Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Autosomal recessive cerebellar ataxia not specified	Criteria Provided Conflicting Classifications	CA5653201	rs_758757135	2 SubmittersRCV001108144 RCV001108145 RCV001108146 RCV001108147 RCV000616455
NM_021830.5(TWNK):c.1070G>C (p.Arg357Pro)	SNV Germline	Chr10:100989280	Conflicting classifications of pathogenicity	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Infantile onset spinocerebellar ataxia Autosomal recessive cerebellar ataxia Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Condition: not provided	Criteria Provided Conflicting Classifications		rs_758026634	3 SubmittersRCV000779014 RCV001102837 RCV001102838 RCV001102839 RCV003222127
NM_002693.3(POLG):c.3630C>A (p.Tyr1210Ter)	SNV Germline	Chr15:89317389	Pathogenic	Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis	Criteria Provided Single Submitter		rs_139562274	1 SubmittersRCV000855761
NM_002693.3(POLG):c.2792T>G (p.Leu931Arg)	SNV Germline	Chr15:89320955	Likely pathogenic	Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis	Criteria Provided Single Submitter		rs_1484810169	1 SubmittersRCV000855755
NM_002693.3(POLG):c.1362G>T (p.Glu454Asp)	SNV Germline	Chr15:89327238	Likely pathogenic	Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis	Criteria Provided Single Submitter		rs_1596358408	1 SubmittersRCV000995843
NM_021830.5(TWNK):c.672T>C (p.Ala224=)	SNV Germline	Chr10:100988882	Conflicting classifications of pathogenicity	Infantile onset spinocerebellar ataxia Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Autosomal recessive cerebellar ataxia Condition: not provided TWNK-related disorder	Criteria Provided Conflicting Classifications		rs_368863664	4 SubmittersRCV001105818 RCV001105817 RCV001105819 RCV001108045 RCV002069743 RCV004538327
NM_021830.5(TWNK):c.1572C>T (p.His524=)	SNV Germline	Chr10:100990523	Conflicting classifications of pathogenicity	Autosomal recessive cerebellar ataxia Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Infantile onset spinocerebellar ataxia Condition: not provided	Criteria Provided Conflicting Classifications		rs_774091248	2 SubmittersRCV001102926 RCV001102928 RCV001102929 RCV001102927 RCV003718320
NM_021830.5(TWNK):c.1597G>A (p.Ala533Thr)	SNV Germline	Chr10:100990873	Conflicting classifications of pathogenicity	Infantile onset spinocerebellar ataxia Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Autosomal recessive cerebellar ataxia Infantile onset spinocerebellar ataxia Perrault syndrome 5 Condition: not provided	Criteria Provided Conflicting Classifications		rs_139124415	3 SubmittersRCV001105993 RCV001105994 RCV001105995 RCV001105996 RCV001839029 RCV002555039
NM_021830.5(TWNK):c.1953G>A (p.Lys651=)	SNV Germline	Chr10:100993408	Conflicting classifications of pathogenicity	Autosomal recessive cerebellar ataxia Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Infantile onset spinocerebellar ataxia Condition: not provided	Criteria Provided Conflicting Classifications		rs_771310512	2 SubmittersRCV001104944 RCV001104945 RCV001104946 RCV001104947 RCV003106115
NM_002693.3(POLG):c.624C>A (p.Cys208Ter)	SNV Germline	Chr15:89333131	Pathogenic/Likely pathogenic	Progressive sclerosing poliodystrophy Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis	Criteria Provided Multiple Submitters No Conflicts		rs_1159974816	2 SubmittersRCV001918974 RCV003502611
NM_002693.3(POLG):c.1457G>A (p.Trp486Ter)	SNV Germline	Chr15:89327040	Pathogenic	Progressive sclerosing poliodystrophy Progressive sclerosing poliodystrophy Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Mitochondrial DNA depletion syndrome 4b	Criteria Provided Multiple Submitters No Conflicts		rs_2055531147	2 SubmittersRCV001970028 RCV003490974
NM_002693.3(POLG):c.2755A>G (p.Met919Val)	SNV Germline	Chr15:89320992	Likely pathogenic	Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Progressive sclerosing poliodystrophy Mitochondrial DNA depletion syndrome 4b	Criteria Provided Single Submitter			1 SubmittersRCV004574886