| | | | Familial Mediterranean fever | Pathogenic
(Dec 8, 2022) | criteria provided, single submitter |
| - GRCh37:
- Chr1:44684100
- GRCh38:
- Chr1:44218428
| DMAP1 | F171L | Generalized hypotonia, Profound global developmental delay | Uncertain significance
(Apr 29, 2021) | no assertion criteria provided |
| - GRCh37:
- ChrX:149828887
- GRCh38:
- ChrX:150660414
| MTM1 | L430fs, L467fs | Generalized hypotonia | Pathogenic | criteria provided, single submitter |
| - GRCh37:
- Chr9:86588265
- GRCh38:
- Chr9:83973350
| HNRNPK | I127N, I151N | Generalized hypotonia | Likely pathogenic | criteria provided, single submitter |
| - GRCh37:
- Chr4:388344-3872380
| HGFAC, HTT, ADD1, ADRA2C, ATP5ME, DGKQ, DOK7, C4orf48, CPLX1, CRIPAK, CTBP1, FAM193A, FAM53A, FGFR3, FGFRL1, GAK, GRK4, HAUS3, IDUA, LETM1, LRPAP1, MAEA, MFSD10, MSANTD1, MXD4, MYL5, NAT8L, NELFA, NKX1-1, NOP14, NSD2, PCGF3, PDE6B, PIGG, POLN, RGS12, RNF212, RNF4, SH3BP2, SLBP, SLC26A1, SLC49A3, SPON2, TACC3, TMEM129, TMEM175, TNIP2, UVSSA, ZFYVE28, ZNF721 | | Generalized hypotonia, Fetal growth restriction, Renal hypoplasia
| Pathogenic
(Mar 15, 2021) | criteria provided, single submitter |
| - GRCh37:
- Chr12:116484240-116564043
| MED13L | | Generalized hypotonia, Global developmental delay | Pathogenic
(Mar 15, 2021) | criteria provided, single submitter |
| - GRCh37:
- ChrX:61091-787353
| | | Generalized hypotonia, Lissencephaly, Microcephaly,
Corpus callosum, agenesis of | Pathogenic
(Oct 1, 2020) | criteria provided, single submitter |
| - GRCh37:
- ChrX:41365759-41401503
| CASK | | Dystonic disorder, Global developmental delay, Congenital cerebellar hypoplasia,
Visual impairment, Generalized hypotonia | Likely pathogenic | no assertion criteria provided |
| - GRCh37:
- Chr5:138525416-138537243
| SIL1 | | Cataract, Ptosis, Global developmental delay,
Cerebellar atrophy, Generalized hypotonia, Cataract,
Strabismus, Constipation, Urinary incontinence,
Generalized hypotonia, Apraxia ...see more | Pathogenic | no assertion criteria provided |
| - GRCh37:
- Chr15:83349398
- GRCh38:
- Chr15:82680646
| AP3B2, CPEB1-AS1 | K262T, K294T | Abnormality of eye movement, Delayed speech and language development, Autism,
Microcephaly, Global developmental delay, Gastroesophageal reflux,
Abnormality of speech or vocalization, Generalized hypotonia, Hypotonia,
Feeding difficulties, Developmental and epileptic encephalopathy, 48not provided,
...see more | Uncertain significance
(Nov 1, 2022) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr2:56108772
- GRCh38:
- Chr2:55881637
| EFEMP1 | Y205* | Tall stature, Arachnodactyly, Generalized hypotonia,
Joint hypermobility, Accelerated skeletal maturation, Ectropion of lower eyelids,
Diverticulum of bladder, High myopia, Dural ectasia,
Posterolateral diaphragmatic hernia, Pulmonary bullaDolichocephaly,
Inguinal hernia, Scoliosis, ...see more | Pathogenic
(Jul 1, 2019) | criteria provided, single submitter |
| - GRCh37:
- Chr2:56144993-56144997
- GRCh38:
- Chr2:55917858-55917862
| EFEMP1 | M107fs | Tall stature, Arachnodactyly, Generalized hypotonia,
Joint hypermobility, Accelerated skeletal maturation, Ectropion of lower eyelids,
Diverticulum of bladder, High myopia, Dural ectasia,
Posterolateral diaphragmatic hernia, Pulmonary bullaDolichocephaly,
Inguinal hernia, Scoliosis, ...see more | Pathogenic
(Jul 1, 2019) | criteria provided, single submitter |
| - GRCh37:
- Chr14:36143795
- GRCh38:
- Chr14:35674589
| RALGAPA1 | N1535S, N1582S, N1076S, N1089S, N1123S | Infantile spasms, Respiratory distress, Feeding difficulties,
Generalized hypotonia | Pathogenic
(Sep 24, 2019) | criteria provided, single submitter |
| - GRCh37:
- Chr14:36041884
- GRCh38:
- Chr14:35572678
| RALGAPA1 | S1911*, S1958*, S2370*, S1924*, S2417* | Infantile spasms, Respiratory distress, Feeding difficulties,
Generalized hypotonia | Pathogenic
(Sep 24, 2019) | criteria provided, single submitter |
| - GRCh37:
- Chr14:36226052
- GRCh38:
- Chr14:35756846
| RALGAPA1 | E204* | Infantile spasms, Respiratory distress, Feeding difficulties,
Generalized hypotonia | Pathogenic
(Sep 24, 2019) | criteria provided, single submitter |
| - GRCh37:
- Chr14:36096643
- GRCh38:
- Chr14:35627437
| RALGAPA1 | F1711fs, F2123fs, F2170fs, F1664fs, F1677fs | Infantile spasms, Respiratory distress, Feeding difficulties,
Generalized hypotonia | Pathogenic
(Sep 24, 2019) | criteria provided, single submitter |
| - GRCh37:
- Chr14:36217916
- GRCh38:
- Chr14:35748710
| RALGAPA1 | R376* | Infantile spasms, Respiratory distress, Feeding difficulties,
Generalized hypotonia | Pathogenic
(Sep 24, 2019) | criteria provided, single submitter |
| - GRCh37:
- Chr9:135073512-135073513
- GRCh38:
- Chr9:132198125-132198126
| NTNG2 | S126fs | Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia, Areflexia, Stereotypical hand wringing,
Generalized hypotonia, Global developmental delay | Pathogenic
(Dec 23, 2019) | no assertion criteria provided |
| - GRCh37:
- Chr11:72297116
- GRCh38:
- Chr11:72586072
| PDE2A | Q387*, Q394*, Q373*, Q385* | EEG abnormality, Intellectual disability, moderate, Generalized hypotonia,
Chorea, Paroxysmal dystonia, Interictal EEG abnormality
| Pathogenic | criteria provided, single submitter |
| - GRCh37:
- Chr5:139494406
- GRCh38:
- Chr5:140114821
| PURA | E214* | PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, Apnea, Generalized hypotonia,
Limb dystonia | Pathogenic/Likely pathogenic
(Jun 28, 2019) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr4:56236248-56236252
- GRCh38:
- Chr4:55370081-55370085
| SRD5A3, SRD5A3-AS1 | F318fs | SRD5A3-congenital disorder of glycosylation, Kahrizi syndrome, not provided,
Generalized hypotonia, Low-set ears, Hemangioma,
Inborn genetic diseases, SRD5A3-congenital disorder of glycosylation | Uncertain significance
(May 11, 2023) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- ChrX:122613916
- GRCh38:
- ChrX:123480065
| GRIA3 | T776M | not provided, Intellectual disability | Conflicting interpretations of pathogenicity
(Dec 14, 2022) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr8:38027316
- GRCh38:
- Chr8:38169798
| LSM1 | | Hydroureter, Generalized hypotonia, Penile hypospadias,
Neurodevelopmental delay, Cryptorchidism, Constipation,
Triphalangeal thumb, Oligohydramnios, Inguinal hernia,
Feeding difficulties, Fetal pyelectasisPatent ductus arteriosus after premature birth,
Perimembranous ventricular septal defect, Hemivertebrae, Abnormal facial shape,
Strabismus, Intellectual disability, Mitral stenosis,
Bicuspid aortic valve, Complex neurodevelopmental disorder, ...see more | Uncertain significance
(May 28, 2020) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr22:42606538
- GRCh38:
- Chr22:42210532
| TCF20 | Q1592* | Generalized hypotonia, Hypotelorism, Intellectual disability
| Pathogenic
(Nov 6, 2018) | no assertion criteria provided |
| - GRCh37:
- ChrX:149828138
- GRCh38:
- ChrX:150659665
| MTM1 | R421L, R384L | not provided, High palate, Enlarged naris,
Primary microcephaly, Polyhydramnios, Abnormal nostril morphology,
Secondary microcephaly, Diffuse white matter abnormalities, Generalized neonatal hypotonia,
Toe clinodactyly, Abnormal cerebral white matter morphologyGeneralized hypotonia,
Neonatal hypotonia, Decreased fetal movement, See cases,
...see more | Pathogenic/Likely pathogenic
(Dec 21, 2022) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr5:92920994
- GRCh38:
- Chr5:93585288
| NR2F1 | C89R | Polymicrogyria, Generalized hypotonia, Infantile spasms,
Motor delay, Unilateral polymicrogyria, Global developmental delay,
Delayed gross motor development, Gray matter heterotopia, Abnormal cerebral white matter morphology,
Polyphagia, SeizureAbnormal corpus callosum morphology,
Exotropia, ...see more | Uncertain significance | criteria provided, single submitter |
| - GRCh37:
- Chr3:129694684
- GRCh38:
- Chr3:129975841
| TRH | A9T | Generalized hypotonia, Global developmental delay, Chorea,
Seizure, Brachycephaly | Uncertain significance | criteria provided, single submitter |
| - GRCh37:
- Chr3:122000933
- GRCh38:
- Chr3:122282086
| CASR | L538F | Generalized hypotonia, Global developmental delay, Chorea,
Seizure, Brachycephaly | Uncertain significance | criteria provided, single submitter |
| - GRCh37:
- Chr22:29752494
- GRCh38:
- Chr22:29356505
| AP1B1 | E213K, E156K | Sensory neuropathy, Generalized hypotonia, Broad-based gait,
Sensory ataxic neuropathy, Decreased body weight, Impaired distal proprioception,
Sensory ataxia, Failure to thrive | Uncertain significance | criteria provided, single submitter |
| - GRCh37:
- Chr7:114303517-114303518
- GRCh38:
- Chr7:114663462-114663463
| FOXP2 | | Generalized hypotonia, Global developmental delay, Sensory ataxia,
Broad-based gait, Expressive language delay, Seizure,
Single transverse palmar crease | Uncertain significance | criteria provided, single submitter |
| - GRCh37:
- Chr2:220423067
- GRCh38:
- Chr2:219558345
| OBSL1 | W1114* | Coarctation of aorta, Bronchomalacia, Ankyloglossia,
Sagittal craniosynostosis, Heart block, Generalized hypotonia,
Bilateral single transverse palmar creases, Bicoronal synostosis, Atrial septal defect,
Clinodactyly of the 5th finger, Delayed gross motor developmentVentricular septal defect,
not provided, ...see more | Uncertain significance
(Feb 22, 2019) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr2:220424193
- GRCh38:
- Chr2:219559471
| OBSL1 | R994C | Coarctation of aorta, Bronchomalacia, Ankyloglossia,
Sagittal craniosynostosis, Heart block, Generalized hypotonia,
Bilateral single transverse palmar creases, Bicoronal synostosis, Atrial septal defect,
Clinodactyly of the 5th finger, Delayed gross motor developmentVentricular septal defect,
not provided, ...see more | Uncertain significance
(May 15, 2022) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr8:22020207
- GRCh38:
- Chr8:22162694
| SFTPC | L55F | Myopathy, Proximal muscle weakness in upper limbs, Infantile axial hypotonia,
Generalized hypotonia, Neonatal hypotonia, Restrictive ventilatory defect,
Neonatal respiratory distress, Respiratory insufficiency due to muscle weakness, Skeletal myopathy,
Pulmonary alveolar proteinosis, Abnormal pulmonary interstitial morphologyCongenital peripheral neuropathy,
Proximal muscle weakness, Respiratory distress, ...see more | Likely pathogenic | criteria provided, single submitter |
| - GRCh37:
- Chr14:64685197
- GRCh38:
- Chr14:64218479
| SYNE2 | G6542W, G176W, G6519W, G50W | Cardiomyopathy, Glaucoma, Obesity,
Muscle weakness, Generalized hypotonia, Specific learning disability,
Gastroesophageal reflux, Panhypopituitarism, Obstructive sleep apnea syndrome,
Limb-girdle muscle weakness, Emery-Dreifuss muscular dystrophy 5, autosomal dominant ...see more | Uncertain significance
(Jun 1, 2022) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr19:39009932
- GRCh38:
- Chr19:38519292
| RYR1 | R3366L | not provided, Cardiomyopathy, Glaucoma,
Obesity, Muscle weakness, Generalized hypotonia,
Specific learning disability, Gastroesophageal reflux, Panhypopituitarism,
Obstructive sleep apnea syndrome, Limb-girdle muscle weaknessRYR1-Related Disorders,
...see more | Conflicting interpretations of pathogenicity
(Mar 30, 2023) | criteria provided, conflicting interpretations |
| - GRCh37:
- ChrX:135122214-135122230
- GRCh38:
- ChrX:136040055-136040071
| SLC9A6 | | See cases, Pectus excavatum, Deeply set eye,
Generalized hypotonia, Autism, Focal white matter lesions,
Global developmental delay, Short stature, Failure to thrive,
Clinodactyly of the 5th finger, ChoreaAbnormal nonverbal communicative behavior,
Seizure, Esotropia, Secondary microcephaly,
...see more | Likely pathogenic
(Dec 21, 2022) | criteria provided, single submitter |
| - GRCh37:
- ChrX:129147280
- GRCh38:
- ChrX:130013304
| BCORL1 | T178A | Stereotypic movement disorder, Hypoplasia of the corpus callosum, Generalized hypotonia,
Cerebral white matter hypoplasia, Long fingers, Autism,
Autistic behavior, Facial hypotonia, Global developmental delay,
Micrognathia, Abnormal pinna morphologyDelayed speech and language development,
Long toe, Moderate global developmental delay, Abnormal cerebral white matter morphology,
Downturned corners of mouth, Abnormal corpus callosum morphology, Proximal placement of thumb,
Microcephaly, Nystagmus, Downslanted palpebral fissures,
Speech apraxia, Wide intermamillary distance, ...see more | Uncertain significance | criteria provided, single submitter |
| - GRCh37:
- Chr16:3779445
- GRCh38:
- Chr16:3729444
| CREBBP | R1868Q, R1830Q | Rubinstein-Taybi syndrome, Generalized hypotonia, Joint laxity,
High palate, Cerebral white matter atrophy, Atrial septal defect,
Pectus carinatum, Abnormal cerebral white matter morphology, Downturned corners of mouth,
Frontal bossing, Thin upper lip vermilionnot provided,
See cases, ...see more | Pathogenic/Likely pathogenic
(Feb 7, 2023) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr2:189927925
- GRCh38:
- Chr2:189063199
| COL5A2 | M614I | Cerebral white matter atrophy, Generalized hypotonia, Joint laxity,
High palate, Pectus carinatum, Thin upper lip vermilion,
Frontal bossing, Atrial septal defect, Abnormal cerebral white matter morphology,
Downturned corners of mouth | Uncertain significance | criteria provided, single submitter |
| - GRCh37:
- Chr11:6661968
- GRCh38:
- Chr11:6640737
| DCHS1 | E293K | Inborn genetic diseases, not provided, Hypoplasia of the corpus callosum,
Generalized hypotonia, Neonatal hypotonia, Periventricular heterotopia,
Relative macrocephaly, Joint hypermobility, Global developmental delay,
Delayed speech and language development, Abnormal renal pelvis morphologyHypopigmented skin patches,
Abnormal corpus callosum morphology, ...see more | Conflicting interpretations of pathogenicity
(Oct 15, 2022) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr11:6661166
- GRCh38:
- Chr11:6639935
| DCHS1 | S560F | Inborn genetic diseases, not provided, Hypoplasia of the corpus callosum,
Generalized hypotonia, Neonatal hypotonia, Periventricular heterotopia,
Relative macrocephaly, Joint hypermobility, Global developmental delay,
Delayed speech and language development, Abnormal renal pelvis morphologyHypopigmented skin patches,
Abnormal corpus callosum morphology, ...see more | Conflicting interpretations of pathogenicity
(Oct 11, 2022) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr16:9017071
- GRCh38:
- Chr16:8923214
| USP7 | | not provided, Central hypotonia, Delayed eruption of primary teeth,
Generalized hypotonia, Macrocephaly, Complete duplication of proximal phalanx of the thumb,
Moderate global developmental delay | Conflicting interpretations of pathogenicity
(Jan 19, 2023) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr16:9017122
- GRCh38:
- Chr16:8923265
| USP7 | H111Q, H12Q, H53Q, H95Q | Generalized hypotonia, Delayed eruption of primary teeth, Moderate global developmental delay,
Central hypotonia, Macrocephaly, Complete duplication of proximal phalanx of the thumb
| Uncertain significance | criteria provided, single submitter |
| - GRCh37:
- Chr22:42607706-42607707
- GRCh38:
- Chr22:42211700-42211701
| TCF20 | P1203fs | Pectus excavatum, Failure to thrive, Generalized hypotonia,
Intellectual disability, moderate, Ptosis | Pathogenic
(Nov 6, 2018) | criteria provided, single submitter |
| - GRCh37:
- Chr6:31747459
- GRCh38:
- Chr6:31779682
| VARS1 | F1072L | Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy, Generalized hypotonia, Elevated hepatic transaminase,
Delayed speech and language development, Premature birth, Microcephaly,
Intellectual disability, not provided | Conflicting interpretations of pathogenicity
(Feb 1, 2023) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr6:31762930
- GRCh38:
- Chr6:31795153
| VARS1 | A22D | Intellectual disability, Generalized hypotonia, Secondary microcephaly,
Elevated hepatic transaminase, Delayed speech and language development, Premature birth
| Uncertain significance
(Jul 18, 2018) | criteria provided, single submitter |
| - GRCh37:
- Chr2:162280336-162280337
- GRCh38:
- Chr2:161423825-161423826
| TBR1 | Q552fs | Hypoplastic anterior commissure, Hypoplastic hippocampus, Generalized hypotonia,
Cortical dysplasia, Inflexible adherence to routines, Severe global developmental delay,
Gait disturbance, EEG abnormality, Abnormal facial shape,
Absent speech, Severe global developmental delay ...see more | Likely pathogenic
(Dec 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr20:62071009
- GRCh38:
- Chr20:63439656
| KCNQ2 | G290V | Seizure, Generalized hypotonia | Pathogenic
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr8:94817079-94817080
- GRCh38:
- Chr8:93804851-93804852
| TMEM67 | | Nystagmus, Iris coloboma, Generalized hypotonia,
Cerebellar vermis hypoplasia | Likely pathogenic
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr1:151378740
- GRCh38:
- Chr1:151406264
| POGZ | P924fs, P829fs, P862fs, P871fs, P915fs | Hypertelorism, Generalized hypotonia, Sensorineural hearing impairment,
Abnormality of the nail, Severe global developmental delay, Strabismus,
Inability to walk by childhood/adolescence, Decreased lacrimation, Brachycephaly,
High palate, Hypoplasia of the corpus callosumAbsent speech,
Anteverted nares, Wide mouth, Seizure,
Microcephaly, Downturned corners of mouth, ...see more | Pathogenic
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- ChrX:69573536
- GRCh38:
- ChrX:70353686
| KIF4A | R518P | Hypotonia, Generalized hypotonia, Poor motor coordination,
Difficulty walking, Horizontal nystagmus, Gynecomastia,
Obesity, Pes planus, Sleep disturbance,
Delayed speech and language development | Uncertain significance
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr20:47991162
- GRCh38:
- Chr20:49374625
| KCNB1 | R312H | Developmental and epileptic encephalopathy, 26, Difficulty walking, Delayed speech and language development,
Seizure, Generalized hypotonia, Epileptic encephalopathy,
Intellectual disability, Epileptic encephalopathy, Intellectual disability,
not provided | Pathogenic/Likely pathogenic
(Oct 24, 2022) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr19:13341005
- GRCh38:
- Chr19:13230191
| CACNA1A | A1808S, A1807S, A1810S, A1813S | Strabismus, Generalized hypotonia, Global developmental delay
| Likely pathogenic
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- ChrX:76888803
- GRCh38:
- ChrX:77633315
| ATRX | G1676C, G1638C | Absent speech, Low-set, posteriorly rotated ears, Microcephaly,
Short stature, Psychomotor deterioration, Drooling,
Generalized hypotonia | Likely pathogenic
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr11:17474818
- GRCh38:
- Chr11:17453271
| ABCC8 | G342W, G341W | Maturity onset diabetes mellitus in young, Transitory neonatal diabetes mellitus, Broad forehead,
Bilateral cryptorchidism, Hypoglycemia, Retrognathia,
Long philtrum, Triangular face, Pointed chin,
Polyhydramnios, Large fleshy earsGeneralized hypotonia,
Neonatal hypotonia, Large for gestational age, ...see more | Conflicting interpretations of pathogenicity
(Jan 1, 2017) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr1:53676782
- GRCh38:
- Chr1:53211110
| CPT2 | Y479F | Carnitine palmitoyl transferase II deficiency, neonatal form, Carnitine palmitoyltransferase II deficiency, not specified,
not provided, Genu valgum, Myopathic facies,
Generalized hypotonia, Pes planus, Hyperextensibility of the finger joints,
Hyperextensibility at elbow, Hyperextensible hand joints ...see more | Conflicting interpretations of pathogenicity
(Aug 20, 2022) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr8:109990022-110168343
| TRHR | | Cognitive impairment, Intellectual disability, mild, Generalized hypotonia,
Neonatal hypotonia, Global developmental delay, Brachycephaly,
Delayed speech and language development, Motor delay, Abnormality of the eye
| Uncertain significance
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr7:72766313-74133332
| ABHD11, ABHD11-AS1, BAZ1B, BCL7B, BUD23, CLDN3, CLDN4, CLIP2, DNAJC30, EIF4H, ELN, FKBP6, FZD9, GTF2I, GTF2IRD1, LAT2, LIMK1, METTL27, MIR590, MLXIPL, RFC2, STX1A, TBL2, TMEM270, VPS37D | | Generalized hypotonia, Global developmental delay, Abnormal facial shape
| Pathogenic
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr2:60308869-62368583
| USP34, XPO1, BCL11A, C2orf74, CCT4, COMMD1, FAM161A, PAPOLG, PEX13, PUS10, REL, SANBR | | Macrocephaly, Generalized hypotonia, Global developmental delay
| Likely pathogenic
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr22:21081260-21431174
| AIFM3, CRKL, LZTR1, P2RX6, PI4KA, SERPIND1, SLC7A4, SNAP29, THAP7 | | Cognitive impairment, Intellectual disability, mild, Generalized hypotonia,
Neonatal hypotonia, Global developmental delay, Brachycephaly,
Delayed speech and language development, Motor delay, Abnormality of the eye
| Uncertain significance
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr22:18894835-21505417
| COMT, CRKL, SERPIND1, SLC25A1, TSSK2, USP41, TANGO2, TBX1, TMEM191B, DGCR2, DGCR6, DGCR6L, DGCR8, ESS2, GNB1L, GSC2, HIRA, KLHL22, GP1BB, FAM230A, GGTLC3, SLC7A4, SNAP29, TXNRD2, UFD1, THAP7, TRMT2A, CLTCL1, AIFM3, ARVCF, C22orf39, CDC45, CLDN5, LZTR1, MED15, MRPL40, P2RX6, PI4KA, PRODH, RANBP1, RIMBP3, RTL10, RTN4R, SCARF2, SEPTIN5, ZDHHC8, ZNF74 | | Abnormality of the ear, Intellectual disability, mild, Generalized hypotonia,
Attention deficit hyperactivity disorder, Clinodactyly, Pes planus,
High palate, Hypernasal speech, Delayed speech and language development,
Triangular face, Failure to thriveHypotelorism,
Leukopenia, Normocytic anemia, ...see more | Pathogenic
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr1:204682513-212815646
| CR2, CTSE, LAMB3, LEMD1, LPGAT1, SLC26A9, SLC30A1, TRAF5, SLC41A1, SLC45A3, SRGAP2, SYT14, TMCC2, TMEM81, TRAF3IP3, UTP25, YOD1, NUCKS1, PACC1, NFASC, NUAK2, MAPKAPK2, MFSD4A, MIR205, MIR205HG, MIR29B2CHG, MIR29C, NEK2, FAM72A, G0S2, GARIN4, HHAT, FCAMR, FCMR, NENF, DSTYK, DTL, DYRK3, ATF3, EIF2D, ELK4, AVPR1B, C1orf116, C1orf74, C4BPA, C4BPB, CAMK1G, CD34, CD46, CD55, CDK18, CNTN2, CR1, CR1L, HSD11B1, IKBKE, IKBKE-AS1, IL10, IL19, IL20, IL24, INTS7, IRF6, KCNH1, KLHDC8A, PFKFB2, PIGR, PLXNA2, PM20D1, PPP2R5A, RAB29, RASSF5, RBBP5, RCOR3, RD3, RHEX, SERTAD4 | | Intellectual disability, Generalized hypotonia, Global developmental delay
| Pathogenic
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr17:16936603-18184130
| ALKBH5, MIEF2, MIR33B, MPRIP, MYO15A, NT5M, PEMT, RASD1, ATPAF2, COPS3, DRC3, PLD6, RAI1, DRG2, FLCN, FLII, GID4, LLGL1, MED9, SREBF1, TOM1L2, TOP3A | | Brachydactyly, Strabismus, Intellectual disability, severe,
Short nose, Microcephaly, Methemoglobinemia,
Poor speech, Myopia, Generalized hypotonia,
Global developmental delay, Pulmonary artery stenosisAbnormal talus morphology,
Short thumb, Abnormal facial shape, Hyperactivity,
...see more | Pathogenic
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr16:29656684-30197341
| ALDOA, ZG16, KCTD13, DOC2A, GDPD3, KIF22, MAPK3, MAZ, ASPHD1, C16orf54, C16orf92, CDIPT, CORO1A, HIRIP3, INO80E, MVP, PAGR1, PPP4C, PRRT2, QPRT, SEZ6L2, SPN, TAOK2, TBX6, TLCD3B, TMEM219, YPEL3 | | Cognitive impairment, Intellectual disability, mild, Generalized hypotonia,
Neonatal hypotonia, Global developmental delay, Brachycephaly,
Delayed speech and language development, Motor delay, Abnormality of the eye
| Likely pathogenic
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr15:85149690-85666309
| WDR73, ALPK3, NMB, PDE8A, SEC11A, SLC28A1, ZNF592, ZSCAN2 | | Hearing impairment, Generalized hypotonia | Uncertain significance
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr15:30366065-32899558
| CHRFAM7A, ARHGAP11B, CHRNA7, FAN1, GOLGA8H, GOLGA8J, GOLGA8N, GOLGA8O, KLF13, MIR211, MTMR10, OTUD7A, TRPM1 | | Ptosis, Generalized hypotonia, Neonatal hypotonia,
Pes valgus, EEG with generalized slow activity, EEG with periodic abnormalities,
Concave nasal ridge, Broad-based gait, Microretrognathia,
Anteverted nares, Delayed speech and language developmentMotor delay,
Short attention span, ...see more | Pathogenic
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr13:101849920-101885422
| NALCN | | Generalized hypotonia, Global developmental delay | Uncertain significance
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr8:68102960
- GRCh38:
- Chr8:67190725
| ARFGEF1, CSPP1 | E1094G, E1007G, E1061G, E749G, E1034G, E1072G, E1121G, E1099G | Joubert syndrome 21, Generalized hypotonia, Cerebellar vermis hypoplasia,
Oculomotor apraxia, Global developmental delay, Relative macrocephaly,
Congenital ptosis, not provided | Conflicting interpretations of pathogenicity
(Jun 23, 2022) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr8:94777641
- GRCh38:
- Chr8:93765413
| TMEM67 | R172*, R91* | RHYNS syndrome, Meckel syndrome, type 3, Nephronophthisis 11,
Joubert syndrome 6, Bardet-Biedl syndrome 14, COACH syndrome 1,
Meckel-Gruber syndrome, Familial aplasia of the vermis, Meckel syndrome, type 3,
Meckel-Gruber syndrome, Iris colobomaNystagmus,
Generalized hypotonia, Cerebellar vermis hypoplasia, ...see more | Pathogenic/Likely pathogenic
(Jun 23, 2023) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr1:53667997
- GRCh38:
- Chr1:53202325
| CPT2 | K79T | Carnitine palmitoyl transferase II deficiency, severe infantile form, Hyperextensibility at elbow, Genu valgum,
Pes planus, Hyperextensibility of the finger joints, Generalized hypotonia,
Myopathic facies, Hyperextensible hand joints, Carnitine palmitoyltransferase II deficiency,
not provided | Uncertain significance
(Oct 17, 2022) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr15:89862193
- GRCh38:
- Chr15:89318962
| POLG, POLGARF | R1081Q | not provided, Generalized hypotonia, Global developmental delay,
Hypsarrhythmia, Mild microcephaly, Secondary microcephaly,
Posterior plagiocephaly, Visual impairment, Cerebral visual impairment,
Plagiocephaly, Infantile spasmsEpileptic encephalopathy,
Inborn genetic diseases, Progressive sclerosing poliodystrophy, ...see more | Conflicting interpretations of pathogenicity
(Sep 7, 2022) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr15:23890894
- GRCh38:
- Chr15:23645747
| MAGEL2 | Q666fs | not provided, Multiple joint contractures, Ambiguous genitalia,
Ventriculomegaly, Generalized hypotonia | Pathogenic
(Jul 14, 2021) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr18:31323276
- GRCh38:
- Chr18:33743312
| ASXL3 | S1155* | not provided | Pathogenic
(Aug 27, 2019) | criteria provided, single submitter |
| - GRCh37:
- Chr19:50339015-50339016
- GRCh38:
- Chr19:49835758-49835759
| MED25 | Q593fs | Charcot-Marie-Tooth disease type 2, Generalized hypotonia, Sensory ataxic neuropathy,
Failure to thrive, Decreased body weight, Impaired distal proprioception,
Sensory neuropathy, Sensory ataxia, Broad-based gait
| Uncertain significance
(Jul 13, 2021) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr11:6662466
- GRCh38:
- Chr11:6641235
| DCHS1 | V127I | Hypopigmented skin patches, Generalized hypotonia, Neonatal hypotonia,
Periventricular heterotopia, Joint hypermobility, Relative macrocephaly,
Delayed speech and language development, Hypoplasia of the corpus callosum, Abnormal corpus callosum morphology,
Abnormal renal pelvis morphology, Global developmental delaynot provided,
...see more | Benign/Likely benign
(Oct 31, 2022) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr10:131761639-131761642
- GRCh38:
- Chr10:129963375-129963378
| EBF3 | E94fs | Recurrent urinary tract infections, Vesicoureteral reflux, Generalized hypotonia,
Growth abnormality, Abnormal facial shape, Constipation,
Global developmental delay, Hypotonia, ataxia, and delayed development syndrome | Pathogenic
(Feb 7, 2017) | no assertion criteria provided |
| - GRCh37:
- Chr14:74004530-74004543
- GRCh38:
- Chr14:73537826-73537839
| ACOT1, HEATR4 | E137fs | Generalized hypotonia | Pathogenic | no assertion criteria provided |
| - GRCh37:
- Chr22:32914195-32914196
- GRCh38:
- Chr22:32518208-32518209
| SYN3 | P481L, P482L | Cerebellar vermis atrophy, Generalized hypotonia, Visual impairment,
Seizure, Global developmental delay | Pathogenic | no assertion criteria provided |
| - GRCh37:
- Chr2:202539978
- GRCh38:
- Chr2:201675255
| MPP4 | W316R | Wide nasal bridge, Intellectual disability, High palate,
Generalized hypotonia, Seizure, Global developmental delay,
Strabismus | Pathogenic | no assertion criteria provided |
| - GRCh37:
- Chr10:131755564
- GRCh38:
- Chr10:129957300
| EBF3 | G171D | Developmental regression, Renotubular dysgenesis, Broad-based gait,
Neurogenic bladder, Generalized hypotonia | Pathogenic | no assertion criteria provided |
| - GRCh37:
- Chr3:47889727
- GRCh38:
- Chr3:47848237
| DHX30 | R782W, R743W, R754W | Neurodevelopmental disorder with severe motor impairment and absent language, not provided | Pathogenic
(Jan 23, 2023) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr12:23818405
- GRCh38:
- Chr12:23665471
| SOX5 | P289S, P302S, P267S, P292S | Severe global developmental delay, Generalized hypotonia, Epileptic encephalopathy
| Likely pathogenic
(Jun 6, 2014) | criteria provided, single submitter |
| - GRCh37:
- Chr1:12025628
- GRCh38:
- Chr1:11965571
| PLOD1 | W521*, W568* | Narrow chest, Neonatal hypotonia, Umbilical hernia,
Severe global developmental delay, Hydrocephalus, Dolichocephaly,
Macrocephaly at birth, Porencephalic cyst, Generalized neonatal hypotonia,
Bilateral cryptorchidism, Joint hypermobilityShort chin,
Hypoplasia of scrotum, Feeding difficulties, Generalized hypotonia,
Joint hypermobility, Depressed nasal bridge, High palate,
Thoracolumbar scoliosis, Congenital omphalocele, ...see more | Pathogenic
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr12:23908660
- GRCh38:
- Chr12:23755726
| SOX5 | | Lamb-Shaffer syndrome, Aplasia/Hypoplasia of the nails, Generalized hypotonia,
Central hypotonia, Thoracolumbar scoliosis, Strabismus
| Likely pathogenic
(Jan 1, 2016) | criteria provided, single submitter |
| - GRCh37:
- ChrX:25022894-25022897
- GRCh38:
- ChrX:25004777-25004780
| ARX | R527fs | Generalized hypotonia | Likely pathogenic
(May 16, 2016) | no assertion criteria provided |
| - GRCh37:
- Chr6:33409151
- GRCh38:
- Chr6:33441374
| SYNGAP1, SYNGAP1-AS1 | | Intellectual disability, autosomal dominant 5 | Uncertain significance
(Feb 3, 2022) | criteria provided, single submitter |
| - GRCh37:
- Chr3:15676986-15676987
- GRCh38:
- Chr3:15635479-15635480
| BTD | G14fs | Biotinidase deficiency | Pathogenic
(May 28, 2019) | criteria provided, single submitter |
| - GRCh37:
- ChrMT:3624
- GRCh38:
- ChrMT:3624
| MT-ND1 | | Generalized hypotonia, Global developmental delay | Uncertain significance
(Nov 21, 2016) | no assertion criteria provided |
| - GRCh37:
- Chr15:48559858
- GRCh38:
- Chr15:48267661
| SLC12A1 | A752V | not provided, Bartter disease type 1, Decreased body weight,
Generalized hypotonia, Sensory neuropathy, Failure to thrive,
Impaired distal proprioception, Sensory ataxia, Broad-based gait,
Sensory ataxic neuropathy | Uncertain significance
(Aug 9, 2022) | criteria provided, multiple submitters, no conflicts |
| | | | Congenital finger flexion contractures, Pes cavus, Generalized hypotonia,
Joint hypermobility, Microcephaly, Attention deficit hyperactivity disorder,
Hearing abnormality, Specific learning disability, Peripheral neuropathy,
Poor coordination, Autistic behaviorFailure to thrive,
Oral motor hypotonia, Mild global developmental delay, ...see more | Pathogenic
(Aug 20, 2016) | criteria provided, single submitter |
| - GRCh37:
- Chr6:135752420
- GRCh38:
- Chr6:135431282
| AHI1 | V767L | not specified, Familial aplasia of the vermis, Global developmental delay,
Relative macrocephaly, Oculomotor apraxia, Generalized hypotonia,
Cerebellar vermis hypoplasia, Congenital ptosis | Conflicting interpretations of pathogenicity
(Oct 5, 2022) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr6:165863756
- GRCh38:
- Chr6:165450268
| PDE10A | Y107C, Y97C, Y373C | Infantile-onset generalized dyskinesia with orofacial involvement, Global developmental delay, Generalized hypotonia
| Pathogenic/Likely pathogenic
(Apr 29, 2016) | no assertion criteria provided |
| - GRCh37:
- Chr6:105244541
- GRCh38:
- Chr6:104796666
| HACE1 | R269*, R235*, R225*, R101*, R172*, R75*, R8*, R107*, R191* | not provided | Pathogenic
(Aug 20, 2023) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr19:52716329
- GRCh38:
- Chr19:52213076
| PPP2R1A | R258H, R79H | Profound global developmental delay, Generalized hypotonia, Synophrys,
Stereotypic movement disorder, Abnormal nonverbal communicative behavior, Microcephaly,
Abnormal facial shape, Autistic behavior, Brachydactyly,
Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome, not providedSee cases,
...see more | Pathogenic/Likely pathogenic
(Dec 21, 2022) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr6:157528243
- GRCh38:
- Chr6:157207109
| ARID1B | R1990*, R2030*, R1280*, R2060*, R2073*, R2113* | Dysphagia, Short stature, Relative macrocephaly,
Generalized hypotonia, Premature birth, Global developmental delay,
Capillary hemangioma, Congenital talipes calcaneovalgus, Joint hypermobility,
Torticollis, not providedCoffin-Siris syndrome 1,
See cases, ...see more | Pathogenic
(Dec 21, 2022) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr2:179401027
- GRCh38:
- Chr2:178536300
| TTN-AS1, TTN | E31842Q, E33483Q, E30915Q, E24418Q, E24543Q, E24610Q | Cardiovascular phenotype, Autosomal recessive limb-girdle muscular dystrophy type 2J, Tibial muscular dystrophy,
Early-onset myopathy with fatal cardiomyopathy, Dilated cardiomyopathy 1G, Myopathy, myofibrillar, 9, with early respiratory failure,
Hypertrophic cardiomyopathy 9, not specified, not provided,
Early-onset myopathy with fatal cardiomyopathy, Autosomal recessive limb-girdle muscular dystrophy type 2JMyopathy, myofibrillar, 9, with early respiratory failure,
Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Tibial muscular dystrophy,
Dilated cardiomyopathy 1G, Delayed speech and language development, Delayed gross motor development,
Abnormality of eye movement, Generalized hypotonia, Hypotonia,
Abnormality of speech or vocalization, ...see more | Conflicting interpretations of pathogenicity
(Aug 8, 2022) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr2:179401042
- GRCh38:
- Chr2:178536315
| TTN, TTN-AS1 | W31837G, W33478G, W30910G, W24413G, W24605G, W24538G | Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J,
Tibial muscular dystrophy, Early-onset myopathy with fatal cardiomyopathy, Dilated cardiomyopathy 1G,
Myopathy, myofibrillar, 9, with early respiratory failure, Hypertrophic cardiomyopathy 9, not specified,
not provided, Myopathy, myofibrillar, 9, with early respiratory failureCardiovascular phenotype,
Autosomal recessive limb-girdle muscular dystrophy type 2J, Early-onset myopathy with fatal cardiomyopathy, Tibial muscular dystrophy,
Dilated cardiomyopathy 1G, Delayed speech and language development, Delayed gross motor development,
Abnormality of eye movement, Generalized hypotonia, Hypotonia,
Abnormality of speech or vocalization, ...see more | Conflicting interpretations of pathogenicity
(Aug 8, 2022) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr2:179567225
- GRCh38:
- Chr2:178702498
| TTN | R10130H, R9813H, R8886H | Autosomal recessive limb-girdle muscular dystrophy type 2J, Tibial muscular dystrophy, Early-onset myopathy with fatal cardiomyopathy,
Dilated cardiomyopathy 1G, Myopathy, myofibrillar, 9, with early respiratory failure, Hypertrophic cardiomyopathy 9,
not specified, not provided, Early-onset myopathy with fatal cardiomyopathy,
Tibial muscular dystrophy, Myopathy, myofibrillar, 9, with early respiratory failureAutosomal recessive limb-girdle muscular dystrophy type 2J,
Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Dilated cardiomyopathy 1G,
Delayed speech and language development, Delayed gross motor development, Abnormality of eye movement,
Generalized hypotonia, Hypotonia, Abnormality of speech or vocalization,
...see more | Conflicting interpretations of pathogenicity
(Aug 8, 2022) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr9:130423419
- GRCh38:
- Chr9:127661140
| STXBP1 | R122*, R108*, R119* | not provided, Developmental and epileptic encephalopathy, 4, Early infantile epileptic encephalopathy with suppression bursts,
Intellectual disability, Delayed speech and language development, Global developmental delay,
Horizontal nystagmus, Axial hypotonia, Strabismus,
Generalized hypotonia, Infantile spasms ...see more | Pathogenic
(Aug 26, 2022) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- ChrX:18606141
- GRCh38:
- ChrX:18588021
| CDKL5 | Q208* | Developmental and epileptic encephalopathy, 2, Bruxism, Delayed speech and language development,
Stereotypical hand wringing, Stereotypical body rocking, Global developmental delay,
Generalized hypotonia, Seizure, Stereotypic movement disorder
| Pathogenic
(Jan 1, 2017) | criteria provided, multiple submitters, no conflicts |