Aliases & Classifications for Timothy Syndrome

MalaCards integrated aliases for Timothy Syndrome:

Name: Timothy Syndrome 57 12 24 53 25 59 75 29 13 6 15 40 73
Lqt8 57 53 25 59 75
Long Qt Syndrome with Syndactyly 57 53 25 75
Long Qt Syndrome 8 57 53 75
Ts 57 25 75
Long Qt Syndrome-Syndactyly Syndrome 59
Long Qt Syndrome 8; Lqt8 57
Long Qt Syndrome Type 8 59

Characteristics:

Orphanet epidemiological data:

59
timothy syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide);

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
de novo mutation, most patients have a gly406arg mutation in cacna1c
some patients with milder phenotypes exhibit somatic mosaicism


HPO:

32
timothy syndrome:
Mortality/Aging sudden death
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Timothy Syndrome

NIH Rare Diseases : 53 Timothy syndromeis a disorder that affects the heart, digits (toes and fingers), and nervous system (brain and nerves). It is a type of long QT syndrome. Long QT syndrome refers to a prolonged QT interval measurement seen on the electrocardiogram. Symptoms of Timothy syndrome include fusion of the skin between fingers or toes (syndactyly), distinctive facial features, and congenital heart defects. Additional symptoms may include developmental delay, intellectual disability, and autism spectrum disorders. There are two forms of Timothy syndrome, classified based on signs and symptoms. Type 1, known as classic type, includes all of the symptoms described above. Type 2, or atypical type, causes a more severe form of long QT syndrome and does not appear to include syndactyly. Both types are caused by mutations in the CACNA1C gene and are inherited in an autosomal dominant manner. Treatment is focused on managing cardiac symptoms. This might include medications such as beta-blockers, placement of defibrillators, and pacemakers.

MalaCards based summary : Timothy Syndrome, also known as lqt8, is related to atrial fibrillation and long qt syndrome. An important gene associated with Timothy Syndrome is CACNA1C (Calcium Voltage-Gated Channel Subunit Alpha1 C), and among its related pathways/superpathways are CREB Pathway and Sweet Taste Signaling. Affiliated tissues include heart, skin and brain, and related phenotypes are thin upper lip vermilion and round face

Disease Ontology : 12 An autosomal dominant disease that is characterized by cardiac, hand/foot, facial, and neurodevelopmental features. The two forms are type 1 (classic) and type 2, a rare form that has material basis in mutations in a transcript variant of CACNA1C on chromosome 12p13.33.

Genetics Home Reference : 25 Timothy syndrome is a rare disorder that affects many parts of the body including the heart, digits (fingers and toes), and the nervous system.

OMIM : 57 Timothy syndrome is characterized by multiorgan dysfunction, including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities, and autism (Splawski et al., 2004). (601005)

UniProtKB/Swiss-Prot : 75 Timothy syndrome: Disorder characterized by multiorgan dysfunction including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities and autism.

Wikipedia : 76 Timothy syndrome is a rare autosomal dominant disorder characterized by physical malformations, as well... more...

GeneReviews:

Related Diseases for Timothy Syndrome

Diseases related to Timothy Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 73)
# Related Disease Score Top Affiliating Genes
1 atrial fibrillation 28.0 KCNE1 KCNH2 KCNQ1
2 long qt syndrome 27.8 CACNA1C KCNE1 KCNH2 KCNQ1
3 ventricular fibrillation, paroxysmal familial, 1 27.6 CACNA1C KCNE1 KCNH2 KCNQ1
4 gilles de la tourette syndrome 12.0
5 turner syndrome 11.8
6 virus-associated trichodysplasia spinulosa 11.6
7 tuberous sclerosis 1 11.1
8 trichostasis spinulosa 11.1
9 temperature sensitivity complementation, cell cycle specific, k12 11.0
10 albinism, oculocutaneous, type ib 10.9
11 tuberous sclerosis 2 10.9
12 colorectal cancer 10.3
13 gastric cancer 10.1
14 cardiac arrest 10.1
15 neuronitis 10.1
16 right bundle branch block 10.0 CACNA1C CACNB2
17 lung cancer 10.0
18 autism 10.0
19 small cell cancer of the lung 9.9
20 esophagitis 9.9
21 squamous cell carcinoma 9.9
22 adenocarcinoma 9.9
23 breast cancer 9.8
24 esophageal cancer 9.8
25 pancreatic cancer 9.8
26 hepatitis 9.8
27 pancreatitis 9.8
28 autism spectrum disorder 9.8
29 glioma susceptibility 1 9.7
30 premature ovarian failure 1 9.7
31 ovarian cancer 1 9.7
32 human immunodeficiency virus type 1 9.7
33 mutagen sensitivity 9.7
34 tendinopathy 9.7
35 acute lymphocytic leukemia 9.7
36 alcoholic hepatitis 9.7
37 leukemia 9.7
38 liver disease 9.7
39 thrombocytopenia 9.7
40 angiosarcoma 9.7
41 sarcoma 9.7
42 conn's syndrome 9.7
43 neuroendocrine tumor 9.7
44 antiphospholipid syndrome 9.7
45 glioblastoma multiforme 9.7
46 vaccinia 9.7
47 tricuspid valve stenosis 9.7
48 malignant pleural mesothelioma 9.7
49 glioblastoma 9.7
50 granulocytopenia 9.7

Graphical network of the top 20 diseases related to Timothy Syndrome:



Diseases related to Timothy Syndrome

Symptoms & Phenotypes for Timothy Syndrome

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Face:
round face

Skeletal Hands:
cutaneous syndactyly

Neurologic Central Nervous System:
developmental delay
mental retardation (in some patients)
seizures (in some patients)
autism or autism spectrum disorder

Head And Neck Teeth:
small teeth

Cardiovascular Heart:
tetralogy of fallot (rare)
patent foramen ovale (in some patients)
cardiac arrhythmias resulting in sudden death
long qt interval, severe
ventricular tachyarrhythmia
more
Muscle Soft Tissue:
hypotonia (in some patients)

Respiratory Lung:
pneumonia (in some patients)

Endocrine Features:
hypothyroidism (in some patients)

Immunology:
recurrent infections

Skeletal Feet:
cutaneous syndactyly

Head And Neck Mouth:
thin upper lip
receding upper jaw

Head And Neck Nose:
flat nasal bridge

Cardiovascular Vascular:
patent ductus arteriosus (in some patients)
pulmonary hypertension (in some patients)

Respiratory Airways:
bronchitis (in some patients)

Skin Nails Hair Hair:
no hair at birth

Laboratory Abnormalities:
hypocalcemia (in some patients)
hypoglycemia (in some patients)


Clinical features from OMIM:

601005

Human phenotypes related to Timothy Syndrome:

32 (show all 22)
# Description HPO Frequency HPO Source Accession
1 thin upper lip vermilion 32 HP:0000219
2 round face 32 HP:0000311
3 microdontia 32 HP:0000691
4 hypothyroidism 32 occasional (7.5%) HP:0000821
5 syndactyly 32 HP:0001159
6 intellectual disability 32 occasional (7.5%) HP:0001249
7 seizures 32 occasional (7.5%) HP:0001250
8 global developmental delay 32 HP:0001263
9 generalized hypotonia 32 occasional (7.5%) HP:0001290
10 ventricular septal defect 32 occasional (7.5%) HP:0001629
11 tetralogy of fallot 32 occasional (7.5%) HP:0001636
12 cardiomegaly 32 occasional (7.5%) HP:0001640
13 patent ductus arteriosus 32 occasional (7.5%) HP:0001643
14 patent foramen ovale 32 occasional (7.5%) HP:0001655
15 prolonged qt interval 32 HP:0001657
16 hypoglycemia 32 occasional (7.5%) HP:0001943
17 pneumonia 32 occasional (7.5%) HP:0002090
18 recurrent infections 32 HP:0002719
19 hypocalcemia 32 occasional (7.5%) HP:0002901
20 depressed nasal bridge 32 HP:0005280
21 bronchitis 32 occasional (7.5%) HP:0012387
22 cutaneous syndactyly 32 HP:0012725

MGI Mouse Phenotypes related to Timothy Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.02 CACNA1C CACNA2D1 CACNB2 KCNH2 KCNQ1

Drugs & Therapeutics for Timothy Syndrome

Search Clinical Trials , NIH Clinical Center for Timothy Syndrome

Genetic Tests for Timothy Syndrome

Genetic tests related to Timothy Syndrome:

# Genetic test Affiliating Genes
1 Timothy Syndrome 29 CACNA1C

Anatomical Context for Timothy Syndrome

MalaCards organs/tissues related to Timothy Syndrome:

41
Heart, Skin, Brain

Publications for Timothy Syndrome

Articles related to Timothy Syndrome:

(show all 49)
# Title Authors Year
1
Timothy syndrome-like condition with syndactyly but without prolongation of the QT interval. ( 29736926 )
2018
2
Inhibition of CDK5 Alleviates the Cardiac Phenotypes in Timothy Syndrome. ( 28648896 )
2017
3
Auditory processing enhancements in the TS2-neo mouse model of Timothy Syndrome, a rare genetic disorder associated with autism spectrum disorders. ( 29159279 )
2017
4
A multicentre study of patients with Timothy syndrome. ( 28371864 )
2017
5
Incomplete Timothy syndrome secondary to a mosaic mutation of the CACNA1C gene diagnosed using next-generation sequencing. ( 27868338 )
2017
6
Timothy syndrome 1 genotype without syndactyly and major extracardiac manifestations. ( 28211989 )
2017
7
Altered Cav1.2 function in the Timothy syndrome mouse model produces ascending serotonergic abnormalities. ( 28921675 )
2017
8
A case report: Is mexiletine usage effective in the shortening of QTC interval and improving the T-wave alternans in Timothy syndrome? ( 29194862 )
2017
9
Cardiac arrest refractory to standard intervention in atypical Timothy syndrome (LQT8 type 2). ( 27034553 )
2016
10
Arrhythmogenesis in Timothy Syndrome is associated with defects in Ca(2+)-dependent inactivation. ( 26822303 )
2016
11
A case of Timothy syndrome with adrenal medullary dystrophy. ( 27593853 )
2016
12
Unusual retrospective prenatal findings in a male newborn with Timothy syndrome type 1. ( 25882468 )
2015
13
A rare association with suffered cardiac arrest, long QT interval, and syndactyly: Timothy syndrome (LQT-8). ( 26301350 )
2015
14
Long QT syndrome with craniofacial, digital, and neurologic features: Is it useful to distinguish between timothy syndrome types 1 and 2? ( 26227324 )
2015
15
Gain-of-function mutations in the calcium channel CACNA1C (Cav1.2) cause non-syndromic long-QT but not Timothy syndrome. ( 25633834 )
2015
16
Expanding the phenotype of Timothy syndrome type 2: an adolescent with ventricular fibrillation but normal development. ( 25691416 )
2015
17
Alteration in basal and depolarization induced transcriptional network in iPSC derived neurons from Timothy syndrome. ( 25360157 )
2014
18
Dentition abnormalities in a Timothy syndrome patient with a novel genetic mutation: a case report. ( 24960393 )
2014
19
Cellular mechanisms of ventricular arrhythmias in a mouse model of Timothy syndrome (long QT syndrome 8). ( 24215710 )
2014
20
Timothy Syndrome: A Life-Threatening Syndactyly Association: A Case Report. ( 29252561 )
2014
21
Exome sequencing helped the fine diagnosis of two siblings afflicted with atypical Timothy syndrome (TS2). ( 24773605 )
2014
22
Novel Timothy syndrome mutation leading to increase in CACNA1C window current. ( 25260352 )
2014
23
Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons. ( 23313911 )
2013
24
Modeling Timothy syndrome with iPS cells. ( 23299782 )
2013
25
Sudden cardiac arrest during anesthesia in a 30-month-old boy with syndactyly: a case of genetically proven Timothy syndrome. ( 23678275 )
2013
26
Inhibition of late sodium current by mexiletine: a novel pharmotherapeutical approach in timothy syndrome. ( 23580742 )
2013
27
Maternal mosaicism confounds the neonatal diagnosis of type 1 Timothy syndrome. ( 23690510 )
2013
28
L-type Ca2+ channel function during Timothy syndrome. ( 22999068 )
2012
29
Ranolazine safely decreases ventricular and atrial fibrillation in Timothy syndrome (LQT8). ( 20883512 )
2012
30
Ca(V)1.2 I-II linker structure and Timothy syndrome. ( 22990809 )
2012
31
Two mechanistically distinct effects of dihydropyridine nifedipine on CaV1.2 L-type CaA^a8_ channels revealed by Timothy syndrome mutation. ( 22554770 )
2012
32
A Mouse Model of Timothy Syndrome: a Complex Autistic Disorder Resulting from a Point Mutation in Cav1.2. ( 24371506 )
2012
33
Case scenario: anesthesia-related cardiac arrest in a child with Timothy syndrome. ( 23011317 )
2012
34
Long QT, syndactyly, joint contractures, stroke and novel CACNA1C mutation: expanding the spectrum of Timothy syndrome. ( 22106044 )
2012
35
Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. ( 22120178 )
2011
36
Somatic mosaicism contributes to phenotypic variation in Timothy syndrome. ( 21910241 )
2011
37
A rare association of long QT syndrome and syndactyly: Timothy syndrome (LQT 8). ( 21915623 )
2011
38
Mouse model of Timothy syndrome recapitulates triad of autistic traits. ( 21878566 )
2011
39
Restoration of normal L-type Ca2+ channel function during Timothy syndrome by ablation of an anchoring protein. ( 21700933 )
2011
40
Increased coupled gating of L-type Ca2+ channels during hypertension and Timothy syndrome. ( 20110531 )
2010
41
The Timothy syndrome mutation of cardiac CaV1.2 (L-type) channels: multiple altered gating mechanisms and pharmacological restoration of inactivation. ( 19074970 )
2009
42
Proarrhythmic defects in Timothy syndrome require calmodulin kinase II. ( 19001023 )
2008
43
Introduction into Ca(v)2.1 of the homologous mutation of Ca(v)1.2 causing the Timothy syndrome questions the role of V421 in the phenotypic definition of P-type Ca(2+) channel. ( 18536931 )
2008
44
The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels. ( 18250309 )
2008
45
A life-threatening complication of the arterial tourniquet in Timothy syndrome. ( 17474959 )
2007
46
Cellular basis for the electrocardiographic and arrhythmic manifestations of Timothy syndrome: effects of ranolazine. ( 17467634 )
2007
47
Cyclosporin and Timothy syndrome increase mode 2 gating of CaV1.2 calcium channels through aberrant phosphorylation of S6 helices. ( 16537462 )
2006
48
Verapamil decreases ventricular tachyarrhythmias in a patient with Timothy syndrome (LQT8). ( 16876748 )
2006
49
Timothy Syndrome ( 20301577 )
1993

Variations for Timothy Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Timothy Syndrome:

75 (show all 11)
# Symbol AA change Variation ID SNP ID
1 CACNA1C p.Gly402Ser VAR_026741
2 CACNA1C p.Gly406Arg VAR_026742
3 CACNA1C p.Ile1186Thr VAR_072381
4 CACNA1C p.Arg518Cys VAR_075154
5 CACNA1C p.Arg518His VAR_075155
6 CACNA1C p.Ala582Asp VAR_075156
7 CACNA1C p.Arg858His VAR_075158
8 CACNA1C p.Arg860Gly VAR_075159
9 CACNA1C p.Ile1186Val VAR_075160
10 CACNA1C p.Ile1523Met VAR_075162
11 CACNA1C p.Glu1544Lys VAR_075163

ClinVar genetic disease variations for Timothy Syndrome:

6
(show top 50) (show all 370)
# Gene Variation Type Significance SNP ID Assembly Location
1 CACNA1C NM_000719.6(CACNA1C): c.1216G> A (p.Gly406Arg) single nucleotide variant Pathogenic rs79891110 GRCh37 Chromosome 12, 2614110: 2614110
2 CACNA1C NM_000719.6(CACNA1C): c.1216G> A (p.Gly406Arg) single nucleotide variant Pathogenic rs79891110 GRCh38 Chromosome 12, 2504944: 2504944
3 CACNA1C NM_000719.6(CACNA1C): c.1204G> A (p.Gly402Ser) single nucleotide variant Pathogenic rs80315385 GRCh37 Chromosome 12, 2614098: 2614098
4 CACNA1C NM_000719.6(CACNA1C): c.1204G> A (p.Gly402Ser) single nucleotide variant Pathogenic rs80315385 GRCh38 Chromosome 12, 2504932: 2504932
5 CACNA1C NM_000719.6(CACNA1C): c.1176G> T (p.Gly392=) single nucleotide variant Conflicting interpretations of pathogenicity rs1051360 GRCh37 Chromosome 12, 2614070: 2614070
6 CACNA1C NM_000719.6(CACNA1C): c.1176G> T (p.Gly392=) single nucleotide variant Conflicting interpretations of pathogenicity rs1051360 GRCh38 Chromosome 12, 2504904: 2504904
7 CACNA1C NM_000719.6(CACNA1C): c.3049-10C> T single nucleotide variant Conflicting interpretations of pathogenicity rs186741807 GRCh37 Chromosome 12, 2714835: 2714835
8 CACNA1C NM_000719.6(CACNA1C): c.3049-10C> T single nucleotide variant Conflicting interpretations of pathogenicity rs186741807 GRCh38 Chromosome 12, 2605669: 2605669
9 CACNA1C NM_000719.6(CACNA1C): c.4140+4G> A single nucleotide variant Conflicting interpretations of pathogenicity rs111442547 GRCh37 Chromosome 12, 2763070: 2763070
10 CACNA1C NM_000719.6(CACNA1C): c.4140+4G> A single nucleotide variant Conflicting interpretations of pathogenicity rs111442547 GRCh38 Chromosome 12, 2653904: 2653904
11 CACNA1C NM_000719.6(CACNA1C): c.202G> A (p.Ala68Thr) single nucleotide variant Uncertain significance rs752000790 GRCh37 Chromosome 12, 2224542: 2224542
12 CACNA1C NM_000719.6(CACNA1C): c.202G> A (p.Ala68Thr) single nucleotide variant Uncertain significance rs752000790 GRCh38 Chromosome 12, 2115376: 2115376
13 CACNA1C NM_000719.6(CACNA1C): c.911T> C (p.Ile304Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs201756421 GRCh37 Chromosome 12, 2595423: 2595423
14 CACNA1C NM_000719.6(CACNA1C): c.911T> C (p.Ile304Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs201756421 GRCh38 Chromosome 12, 2486257: 2486257
15 CACNA1C NM_001167625.1(CACNA1C): c.1216G> A (p.Gly406Arg) single nucleotide variant Pathogenic rs786205745 GRCh37 Chromosome 12, 2613704: 2613704
16 CACNA1C NM_001167625.1(CACNA1C): c.1216G> A (p.Gly406Arg) single nucleotide variant Pathogenic rs786205745 GRCh38 Chromosome 12, 2504538: 2504538
17 CACNA1C NM_001167623.1(CACNA1C): c.1216G> C (p.Gly406Arg) single nucleotide variant Pathogenic rs786205745 GRCh37 Chromosome 12, 2613704: 2613704
18 CACNA1C NM_001167623.1(CACNA1C): c.1216G> C (p.Gly406Arg) single nucleotide variant Pathogenic rs786205745 GRCh38 Chromosome 12, 2504538: 2504538
19 CACNA1C NM_000719.6(CACNA1C): c.1486C> T (p.Arg496Trp) single nucleotide variant Uncertain significance rs760888275 GRCh37 Chromosome 12, 2666121: 2666121
20 CACNA1C NM_000719.6(CACNA1C): c.1486C> T (p.Arg496Trp) single nucleotide variant Uncertain significance rs760888275 GRCh38 Chromosome 12, 2556955: 2556955
21 CACNA1C NM_000719.6(CACNA1C): c.1864G> A (p.Val622Ile) single nucleotide variant Uncertain significance rs768270021 GRCh37 Chromosome 12, 2676929: 2676929
22 CACNA1C NM_000719.6(CACNA1C): c.1864G> A (p.Val622Ile) single nucleotide variant Uncertain significance rs768270021 GRCh38 Chromosome 12, 2567763: 2567763
23 CACNA1C NM_000719.6(CACNA1C): c.2067C> T (p.Phe689=) single nucleotide variant Conflicting interpretations of pathogenicity rs112170830 GRCh37 Chromosome 12, 2690927: 2690927
24 CACNA1C NM_000719.6(CACNA1C): c.2067C> T (p.Phe689=) single nucleotide variant Conflicting interpretations of pathogenicity rs112170830 GRCh38 Chromosome 12, 2581761: 2581761
25 CACNA1C NM_000719.6(CACNA1C): c.3862G> A (p.Ala1288Thr) single nucleotide variant Uncertain significance rs367895193 GRCh37 Chromosome 12, 2743496: 2743496
26 CACNA1C NM_000719.6(CACNA1C): c.3862G> A (p.Ala1288Thr) single nucleotide variant Uncertain significance rs367895193 GRCh38 Chromosome 12, 2634330: 2634330
27 CACNA1C NM_000719.6(CACNA1C): c.4727-9G> A single nucleotide variant Conflicting interpretations of pathogenicity rs757966245 GRCh37 Chromosome 12, 2783698: 2783698
28 CACNA1C NM_000719.6(CACNA1C): c.4727-9G> A single nucleotide variant Conflicting interpretations of pathogenicity rs757966245 GRCh38 Chromosome 12, 2674532: 2674532
29 CACNA1C NM_000719.6(CACNA1C): c.5383G> A (p.Gly1795Arg) single nucleotide variant Benign/Likely benign rs111298509 GRCh38 Chromosome 12, 2679735: 2679735
30 CACNA1C NM_000719.6(CACNA1C): c.5383G> A (p.Gly1795Arg) single nucleotide variant Benign/Likely benign rs111298509 GRCh37 Chromosome 12, 2788901: 2788901
31 CACNA1C; CACNA1C-AS1 NM_000719.6(CACNA1C): c.5593G> A (p.Glu1865Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs200231105 GRCh38 Chromosome 12, 2685755: 2685755
32 CACNA1C; CACNA1C-AS1 NM_000719.6(CACNA1C): c.5593G> A (p.Glu1865Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs200231105 GRCh37 Chromosome 12, 2794921: 2794921
33 CACNA1C NM_000719.6(CACNA1C): c.5731G> C (p.Gly1911Arg) single nucleotide variant Uncertain significance rs374528680 GRCh38 Chromosome 12, 2686216: 2686216
34 CACNA1C NM_000719.6(CACNA1C): c.5731G> C (p.Gly1911Arg) single nucleotide variant Uncertain significance rs374528680 GRCh37 Chromosome 12, 2795382: 2795382
35 CACNA1C NM_000719.6(CACNA1C): c.6344G> C (p.Gly2115Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs199694744 GRCh38 Chromosome 12, 2691126: 2691126
36 CACNA1C NM_000719.6(CACNA1C): c.6344G> C (p.Gly2115Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs199694744 GRCh37 Chromosome 12, 2800292: 2800292
37 CACNA1C NM_000719.6(CACNA1C): c.3234C> T (p.Asp1078=) single nucleotide variant Conflicting interpretations of pathogenicity rs111606207 GRCh37 Chromosome 12, 2716174: 2716174
38 CACNA1C NM_000719.6(CACNA1C): c.3234C> T (p.Asp1078=) single nucleotide variant Conflicting interpretations of pathogenicity rs111606207 GRCh38 Chromosome 12, 2607008: 2607008
39 CACNA1C NM_000719.6(CACNA1C): c.4418C> G (p.Ala1473Gly) single nucleotide variant Likely pathogenic rs794727587 GRCh37 Chromosome 12, 2774766: 2774766
40 CACNA1C NM_000719.6(CACNA1C): c.4418C> G (p.Ala1473Gly) single nucleotide variant Likely pathogenic rs794727587 GRCh38 Chromosome 12, 2665600: 2665600
41 CACNA1C NM_000719.6(CACNA1C): c.4942G> A (p.Ala1648Thr) single nucleotide variant Uncertain significance rs370432385 GRCh37 Chromosome 12, 2786373: 2786373
42 CACNA1C NM_000719.6(CACNA1C): c.4942G> A (p.Ala1648Thr) single nucleotide variant Uncertain significance rs370432385 GRCh38 Chromosome 12, 2677207: 2677207
43 CACNA1C NM_000719.6(CACNA1C): c.5644T> C (p.Ser1882Pro) single nucleotide variant Conflicting interpretations of pathogenicity rs369438564 GRCh37 Chromosome 12, 2794972: 2794972
44 CACNA1C NM_000719.6(CACNA1C): c.5644T> C (p.Ser1882Pro) single nucleotide variant Conflicting interpretations of pathogenicity rs369438564 GRCh38 Chromosome 12, 2685806: 2685806
45 CACNA1C NM_000719.6(CACNA1C): c.6161A> G (p.Lys2054Arg) single nucleotide variant Uncertain significance rs200588235 GRCh37 Chromosome 12, 2800109: 2800109
46 CACNA1C NM_000719.6(CACNA1C): c.6161A> G (p.Lys2054Arg) single nucleotide variant Uncertain significance rs200588235 GRCh38 Chromosome 12, 2690943: 2690943
47 CACNA1C NM_000719.6(CACNA1C): c.6272A> G (p.Asn2091Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs201090446 GRCh37 Chromosome 12, 2800220: 2800220
48 CACNA1C NM_000719.6(CACNA1C): c.6272A> G (p.Asn2091Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs201090446 GRCh38 Chromosome 12, 2691054: 2691054
49 CACNA1C NM_000719.6(CACNA1C): c.3114G> C (p.Leu1038=) single nucleotide variant Benign/Likely benign rs114139824 GRCh37 Chromosome 12, 2714910: 2714910
50 CACNA1C NM_000719.6(CACNA1C): c.3114G> C (p.Leu1038=) single nucleotide variant Benign/Likely benign rs114139824 GRCh38 Chromosome 12, 2605744: 2605744

Expression for Timothy Syndrome

Search GEO for disease gene expression data for Timothy Syndrome.

Pathways for Timothy Syndrome

Pathways related to Timothy Syndrome according to GeneCards Suite gene sharing:

(show all 24)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.99 CACNA1C CACNA2D1 CACNB2 CAMK2G
2
Show member pathways
12.76 CACNA1C CACNA2D1 CACNB2 CAMK2G
3
Show member pathways
12.71 CACNA2D1 CACNB2 CAMK2G KCNH2 KCNQ1
4
Show member pathways
12.71 CACNA1C CACNA2D1 CACNB2 CAMK2G KCNE1 KCNQ1
5
Show member pathways
12.65 CACNA1C CACNA2D1 CACNB2 CAMK2G
6
Show member pathways
12.58 CACNA1C CACNA2D1 CACNB2 CAMK2G
7 12.46 CACNA1C CACNA2D1 CACNB2
8
Show member pathways
12.44 CACNA1C CACNA2D1 CACNB2 CAMK2G
9
Show member pathways
12.43 CACNA1C CACNA2D1 CACNB2 CAMK2G KCNE1 KCNH2
10
Show member pathways
12.28 CACNA1C CACNB2 CAMK2G
11
Show member pathways
12.24 CACNA1C CACNA2D1 CACNB2
12
Show member pathways
12.16 CACNA1C CACNA2D1 CACNB2
13 12.08 CACNA1C CACNB2 KCNE1 KCNH2 KCNQ1
14
Show member pathways
12.03 CACNA1C CACNA2D1 CACNB2 CAMK2G
15
Show member pathways
11.96 CACNA1C CACNA2D1 CACNB2
16 11.85 CACNA1C CACNA2D1 CACNB2
17
Show member pathways
11.8 CACNA1C CACNA2D1 CACNB2
18 11.55 CACNA1C CACNA2D1 CACNB2
19 11.32 CACNA1C CACNA2D1 CACNB2 KCNQ1
20 11.3 CACNA1C CACNA2D1 CACNB2
21 11.16 CACNA1C CACNB2
22 11.1 CACNA1C CACNB2 KCNE1 KCNH2 KCNQ1
23
Show member pathways
10.98 CACNA1C CACNA2D1 CACNB2 CAMK2G KCNE1 KCNQ1
24 10.84 KCNE1 KCNQ1

GO Terms for Timothy Syndrome

Cellular components related to Timothy Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 9.8 CACNA1C CACNA2D1 CACNB2 CAMK2G KCNE1 KCNH2
2 voltage-gated potassium channel complex GO:0008076 9.33 KCNE1 KCNH2 KCNQ1
3 sarcoplasmic reticulum GO:0016529 9.32 CACNA2D1 CAMK2G
4 voltage-gated calcium channel complex GO:0005891 9.13 CACNA1C CACNA2D1 CACNB2
5 L-type voltage-gated calcium channel complex GO:1990454 8.8 CACNA1C CACNA2D1 CACNB2

Biological processes related to Timothy Syndrome according to GeneCards Suite gene sharing:

(show all 31)
# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.93 CACNA1C CACNA2D1 CACNB2 KCNE1 KCNH2 KCNQ1
2 calcium ion transport GO:0006816 9.85 CACNA1C CACNA2D1 CACNB2 CAMK2G
3 potassium ion transport GO:0006813 9.79 KCNE1 KCNH2 KCNQ1
4 potassium ion transmembrane transport GO:0071805 9.78 KCNE1 KCNH2 KCNQ1
5 calcium ion transmembrane transport GO:0070588 9.77 CACNA1C CACNA2D1 CACNB2
6 cardiac muscle cell action potential involved in contraction GO:0086002 9.71 CACNA1C CACNA2D1 KCNE1
7 positive regulation of potassium ion transmembrane transport GO:1901381 9.7 KCNE1 KCNH2 KCNQ1
8 ventricular cardiac muscle cell action potential GO:0086005 9.69 KCNE1 KCNH2 KCNQ1
9 regulation of membrane repolarization GO:0060306 9.67 KCNE1 KCNH2 KCNQ1
10 cellular response to drug GO:0035690 9.65 KCNH2 KCNQ1
11 cellular response to cAMP GO:0071320 9.65 KCNE1 KCNQ1
12 membrane repolarization GO:0086009 9.65 KCNE1 KCNH2 KCNQ1
13 cardiac muscle contraction GO:0060048 9.64 KCNH2 KCNQ1
14 membrane depolarization during action potential GO:0086010 9.64 CACNA1C KCNH2
15 regulation of calcium ion transport GO:0051924 9.63 CACNA2D1 CAMK2G
16 calcium ion import GO:0070509 9.63 CACNA1C CACNB2
17 regulation of ion transmembrane transport GO:0034765 9.63 CACNA1C CACNA2D1 CACNB2 KCNE1 KCNH2 KCNQ1
18 regulation of potassium ion transmembrane transport GO:1901379 9.62 KCNE1 KCNH2
19 calcium ion transport into cytosol GO:0060402 9.62 CACNA1C CACNA2D1
20 membrane repolarization during cardiac muscle cell action potential GO:0086013 9.61 KCNE1 KCNH2 KCNQ1
21 membrane depolarization during AV node cell action potential GO:0086045 9.59 CACNA1C CACNB2
22 potassium ion export across plasma membrane GO:0097623 9.58 KCNH2 KCNQ1
23 positive regulation of high voltage-gated calcium channel activity GO:1901843 9.58 CACNA2D1 CACNB2
24 potassium ion export GO:0071435 9.58 KCNE1 KCNH2 KCNQ1
25 calcium ion transmembrane transport via high voltage-gated calcium channel GO:0061577 9.57 CACNA1C CACNA2D1
26 membrane depolarization during atrial cardiac muscle cell action potential GO:0098912 9.56 CACNA1C CACNB2
27 regulation of ventricular cardiac muscle cell membrane repolarization GO:0060307 9.56 CACNA2D1 KCNE1 KCNH2 KCNQ1
28 membrane repolarization during ventricular cardiac muscle cell action potential GO:0098915 9.54 KCNE1 KCNH2 KCNQ1
29 membrane repolarization during action potential GO:0086011 9.5 KCNE1 KCNH2 KCNQ1
30 cardiac conduction GO:0061337 9.43 CACNA1C CACNA2D1 CACNB2 KCNE1 KCNH2 KCNQ1
31 regulation of heart rate by cardiac conduction GO:0086091 9.1 CACNA1C CACNA2D1 CACNB2 KCNE1 KCNH2 KCNQ1

Molecular functions related to Timothy Syndrome according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 calmodulin binding GO:0005516 9.69 CACNA1C CAMK2G KCNQ1
2 voltage-gated ion channel activity GO:0005244 9.65 CACNA1C KCNH2 KCNQ1
3 calcium channel activity GO:0005262 9.63 CACNA1C CACNA2D1 CACNB2
4 potassium channel activity GO:0005267 9.61 KCNE1 KCNH2 KCNQ1
5 voltage-gated potassium channel activity GO:0005249 9.58 KCNE1 KCNH2 KCNQ1
6 scaffold protein binding GO:0097110 9.52 KCNH2 KCNQ1
7 voltage-gated calcium channel activity GO:0005245 9.5 CACNA1C CACNA2D1 CACNB2
8 high voltage-gated calcium channel activity GO:0008331 9.49 CACNA1C CACNB2
9 delayed rectifier potassium channel activity GO:0005251 9.43 KCNE1 KCNH2 KCNQ1
10 voltage-gated calcium channel activity involved in AV node cell action potential GO:0086056 9.37 CACNA1C CACNB2
11 voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization GO:1902282 9.33 KCNE1 KCNH2 KCNQ1
12 voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization GO:0086008 9.13 KCNE1 KCNH2 KCNQ1
13 voltage-gated calcium channel activity involved in cardiac muscle cell action potential GO:0086007 8.8 CACNA1C CACNA2D1 CACNB2

Sources for Timothy Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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