TS
MCID: TMT001
MIFTS: 53

Timothy Syndrome (TS)

Categories: Genetic diseases, Immune diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Timothy Syndrome

MalaCards integrated aliases for Timothy Syndrome:

Name: Timothy Syndrome 57 12 24 53 25 59 75 29 13 6 44 15 40 73
Long Qt Syndrome with Syndactyly 57 24 53 25 75
Lqt8 57 53 25 59 75
Long Qt Syndrome 8 57 53 75
Ts 57 25 75
Long Qt Syndrome Type 8 24 59
Long Qt Syndrome-Syndactyly Syndrome 59
Long Qt Syndrome 8; Lqt8 57

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


GeneReviews:

24
Penetrance No study has specifically investigated the issue of the penetrance of ts. of note, however, penetrance was 100% in the 18 affected individuals with timothy syndrome reported to date [splawski et al 2004, lo-a-njoe et al 2005, splawski et al 2005] and it has remained very high (22 of 23 individuals with pathogenic variants had clearly abnormal electrocardiogram) in the two reports of gain-of-function cacn1c pathogenic variants in association with qt prolongation without extracardiac abnormalities [fukuyama et al 2014, wemhöner et al 2015]...

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 long qt syndrome with syndactyly, is related to cardiac arrest and atrial fibrillation. An important gene associated with Timothy Syndrome is CACNA1C (Calcium Voltage-Gated Channel Subunit Alpha1 C), and among its related pathways/superpathways are Integrin Pathway and CREB Pathway. Affiliated tissues include heart, skin and brain, and related phenotypes are hypothyroidism and intellectual disability

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: NBK1403

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 100)
# Related Disease Score Top Affiliating Genes
1 cardiac arrest 29.8 CACNB2 KCNH2 KCNQ1
2 atrial fibrillation 29.4 KCNE1 KCNH2 KCNQ1
3 long qt syndrome 29.3 CACNA1C CACNB2 KCNE1 KCNH2 KCNQ1
4 ventricular fibrillation, paroxysmal familial, 1 29.2 CACNA1C KCNE1 KCNH2 KCNQ1
5 gilles de la tourette syndrome 12.1
6 turner syndrome 11.9
7 virus-associated trichodysplasia spinulosa 11.7
8 tuberous sclerosis 1 11.2
9 trichostasis spinulosa 11.2
10 temperature sensitivity complementation, cell cycle specific, k12 11.2
11 albinism, oculocutaneous, type ib 11.0
12 tuberous sclerosis 2 11.0
13 colorectal cancer 10.4
14 gastric cancer 10.2
15 obsessive-compulsive disorder 10.2
16 adenocarcinoma 10.2
17 chromosome 2q35 duplication syndrome 10.1
18 autism 10.1
19 carney complex, type 1 10.1
20 lung cancer 10.1
21 caronte 10.1
22 breast cancer 10.0
23 small cell cancer of the lung 10.0
24 squamous cell carcinoma 10.0
25 right bundle branch block 10.0 CACNA1C CACNB2
26 pancreatic cancer 9.9
27 pemphigus foliaceus 9.9
28 melanoma 9.9
29 breast adenocarcinoma 9.9
30 spindle cell hemangioma 9.9
31 headache 9.9 CACNA1C CACNB2
32 long qt syndrome 13 9.8 KCNH2 KCNQ1
33 cardiac conduction defect 9.8 KCNH2 KCNQ1
34 esophageal cancer 9.8
35 glioma susceptibility 1 9.8
36 premature chromatid separation trait 9.8
37 retinitis pigmentosa 1 9.8
38 disorganization, mouse, homolog of 9.8
39 arts syndrome 9.8
40 premature ovarian failure 1 9.8
41 alzheimer disease 5 9.8
42 ovarian cancer 1 9.8
43 human immunodeficiency virus type 1 9.8
44 mutagen sensitivity 9.8
45 bone mineral density quantitative trait locus 15 9.8
46 myelodysplastic syndrome 9.8
47 tendinopathy 9.8
48 acute lymphocytic leukemia 9.8
49 alcoholic hepatitis 9.8
50 hepatitis 9.8

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 24)
# Description HPO Frequency HPO Source Accession
1 hypothyroidism 32 occasional (7.5%) HP:0000821
2 intellectual disability 32 occasional (7.5%) HP:0001249
3 seizures 32 occasional (7.5%) HP:0001250
4 global developmental delay 32 HP:0001263
5 depressed nasal bridge 32 HP:0005280
6 cardiomegaly 32 occasional (7.5%) HP:0001640
7 hypoglycemia 32 occasional (7.5%) HP:0001943
8 patent ductus arteriosus 32 occasional (7.5%) HP:0001643
9 microdontia 32 HP:0000691
10 autism 32 HP:0000717
11 prolonged qt interval 32 HP:0001657
12 round face 32 HP:0000311
13 tetralogy of fallot 32 occasional (7.5%) HP:0001636
14 ventricular septal defect 32 occasional (7.5%) HP:0001629
15 hypocalcemia 32 occasional (7.5%) HP:0002901
16 recurrent infections 32 HP:0002719
17 thin upper lip vermilion 32 HP:0000219
18 generalized hypotonia 32 occasional (7.5%) HP:0001290
19 pneumonia 32 occasional (7.5%) HP:0002090
20 syndactyly 32 HP:0001159
21 patent foramen ovale 32 occasional (7.5%) HP:0001655
22 cutaneous syndactyly 32 HP:0012725
23 bronchitis 32 occasional (7.5%) HP:0012387
24 bradycardia 32 HP:0001662

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

Cochrane evidence based reviews: 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, Lung, Liver, Colon

Publications for Timothy Syndrome

Articles related to Timothy Syndrome:

(show top 50) (show all 54)
# Title Authors Year
1
Timothy syndrome-like condition with syndactyly but without prolongation of the QT interval. ( 29736926 )
2018
2
A novel CACNA1C mutation identified in a patient with Timothy syndrome without syndactyly exerts both marked loss- and gain-of-function effects. ( 30023270 )
2018
3
Clinical Outcomes and Modes of Death in Timothy Syndrome: A Multicenter International Study of a Rare Disorder. ( 30067485 )
2018
4
Enhanced oligodendrocyte maturation and myelination in a mouse model of Timothy syndrome. ( 30151840 )
2018
5
Dynamic Electrocardiographic Abnormalities Captured in Timothy Syndrome. ( 30466860 )
2018
6
Inhibition of CDK5 Alleviates the Cardiac Phenotypes in Timothy Syndrome. ( 28648896 )
2017
7
Auditory processing enhancements in the TS2-neo mouse model of Timothy Syndrome, a rare genetic disorder associated with autism spectrum disorders. ( 29159279 )
2017
8
A multicentre study of patients with Timothy syndrome. ( 28371864 )
2017
9
Incomplete Timothy syndrome secondary to a mosaic mutation of the CACNA1C gene diagnosed using next-generation sequencing. ( 27868338 )
2017
10
Timothy syndrome 1 genotype without syndactyly and major extracardiac manifestations. ( 28211989 )
2017
11
Altered Cav1.2 function in the Timothy syndrome mouse model produces ascending serotonergic abnormalities. ( 28921675 )
2017
12
A case report: Is mexiletine usage effective in the shortening of QTC interval and improving the T-wave alternans in Timothy syndrome? ( 29194862 )
2017
13
Cardiac arrest refractory to standard intervention in atypical Timothy syndrome (LQT8 type 2). ( 27034553 )
2016
14
Arrhythmogenesis in Timothy Syndrome is associated with defects in Ca(2+)-dependent inactivation. ( 26822303 )
2016
15
A case of Timothy syndrome with adrenal medullary dystrophy. ( 27593853 )
2016
16
Unusual retrospective prenatal findings in a male newborn with Timothy syndrome type 1. ( 25882468 )
2015
17
A rare association with suffered cardiac arrest, long QT interval, and syndactyly: Timothy syndrome (LQT-8). ( 26301350 )
2015
18
Long QT syndrome with craniofacial, digital, and neurologic features: Is it useful to distinguish between timothy syndrome types 1 and 2? ( 26227324 )
2015
19
Gain-of-function mutations in the calcium channel CACNA1C (Cav1.2) cause non-syndromic long-QT but not Timothy syndrome. ( 25633834 )
2015
20
Expanding the phenotype of Timothy syndrome type 2: an adolescent with ventricular fibrillation but normal development. ( 25691416 )
2015
21
Alteration in basal and depolarization induced transcriptional network in iPSC derived neurons from Timothy syndrome. ( 25360157 )
2014
22
Dentition abnormalities in a Timothy syndrome patient with a novel genetic mutation: a case report. ( 24960393 )
2014
23
Cellular mechanisms of ventricular arrhythmias in a mouse model of Timothy syndrome (long QT syndrome 8). ( 24215710 )
2014
24
Timothy Syndrome: A Life-Threatening Syndactyly Association: A Case Report. ( 29252561 )
2014
25
Exome sequencing helped the fine diagnosis of two siblings afflicted with atypical Timothy syndrome (TS2). ( 24773605 )
2014
26
Novel Timothy syndrome mutation leading to increase in CACNA1C window current. ( 25260352 )
2014
27
Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons. ( 23313911 )
2013
28
Modeling Timothy syndrome with iPS cells. ( 23299782 )
2013
29
Sudden cardiac arrest during anesthesia in a 30-month-old boy with syndactyly: a case of genetically proven Timothy syndrome. ( 23678275 )
2013
30
Inhibition of late sodium current by mexiletine: a novel pharmotherapeutical approach in timothy syndrome. ( 23580742 )
2013
31
Maternal mosaicism confounds the neonatal diagnosis of type 1 Timothy syndrome. ( 23690510 )
2013
32
L-type Ca2+ channel function during Timothy syndrome. ( 22999068 )
2012
33
Ranolazine safely decreases ventricular and atrial fibrillation in Timothy syndrome (LQT8). ( 20883512 )
2012
34
Ca(V)1.2 I-II linker structure and Timothy syndrome. ( 22990809 )
2012
35
Two mechanistically distinct effects of dihydropyridine nifedipine on CaV1.2 L-type CaA^a8_ channels revealed by Timothy syndrome mutation. ( 22554770 )
2012
36
A Mouse Model of Timothy Syndrome: a Complex Autistic Disorder Resulting from a Point Mutation in Cav1.2. ( 24371506 )
2012
37
Long QT, syndactyly, joint contractures, stroke and novel CACNA1C mutation: expanding the spectrum of Timothy syndrome. ( 22106044 )
2012
38
Case scenario: anesthesia-related cardiac arrest in a child with Timothy syndrome. ( 23011317 )
2012
39
Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. ( 22120178 )
2011
40
Somatic mosaicism contributes to phenotypic variation in Timothy syndrome. ( 21910241 )
2011
41
A rare association of long QT syndrome and syndactyly: Timothy syndrome (LQT 8). ( 21915623 )
2011
42
Mouse model of Timothy syndrome recapitulates triad of autistic traits. ( 21878566 )
2011
43
Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. ( 21307850 )
2011
44
Restoration of normal L-type Ca2+ channel function during Timothy syndrome by ablation of an anchoring protein. ( 21700933 )
2011
45
Increased coupled gating of L-type Ca2+ channels during hypertension and Timothy syndrome. ( 20110531 )
2010
46
The Timothy syndrome mutation of cardiac CaV1.2 (L-type) channels: multiple altered gating mechanisms and pharmacological restoration of inactivation. ( 19074970 )
2009
47
Proarrhythmic defects in Timothy syndrome require calmodulin kinase II. ( 19001023 )
2008
48
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
49
The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels. ( 18250309 )
2008
50
A life-threatening complication of the arterial tourniquet in Timothy syndrome. ( 17474959 )
2007

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 449)
# 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.1468G> A (p.Gly490Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs121912775 GRCh37 Chromosome 12, 2659186: 2659186
6 CACNA1C NM_000719.6(CACNA1C): c.1468G> A (p.Gly490Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs121912775 GRCh38 Chromosome 12, 2550020: 2550020
7 CACNA1C NM_000719.6(CACNA1C): c.171C> T (p.Asp57=) single nucleotide variant Benign/Likely benign rs34419050 GRCh37 Chromosome 12, 2224511: 2224511
8 CACNA1C NM_000719.6(CACNA1C): c.171C> T (p.Asp57=) single nucleotide variant Benign/Likely benign rs34419050 GRCh38 Chromosome 12, 2115345: 2115345
9 CACNA1C NM_000719.6(CACNA1C): c.372-15G> A single nucleotide variant Benign/Likely benign rs55792866 GRCh37 Chromosome 12, 2229476: 2229476
10 CACNA1C NM_000719.6(CACNA1C): c.372-15G> A single nucleotide variant Benign/Likely benign rs55792866 GRCh38 Chromosome 12, 2120310: 2120310
11 CACNA1C NM_000719.6(CACNA1C): c.5680+15C> T single nucleotide variant Benign/Likely benign rs114036394 GRCh37 Chromosome 12, 2795023: 2795023
12 CACNA1C NM_000719.6(CACNA1C): c.5680+15C> T single nucleotide variant Benign/Likely benign rs114036394 GRCh38 Chromosome 12, 2685857: 2685857
13 CACNA1C NM_000719.6(CACNA1C): c.6388G> A (p.Asp2130Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs199473392 GRCh37 Chromosome 12, 2800336: 2800336
14 CACNA1C NM_000719.6(CACNA1C): c.6388G> A (p.Asp2130Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs199473392 GRCh38 Chromosome 12, 2691170: 2691170
15 CACNA1C NM_000719.6(CACNA1C): c.3387G> A (p.Thr1129=) single nucleotide variant Benign/Likely benign rs188224114 GRCh37 Chromosome 12, 2717707: 2717707
16 CACNA1C NM_000719.6(CACNA1C): c.3387G> A (p.Thr1129=) single nucleotide variant Benign/Likely benign rs188224114 GRCh38 Chromosome 12, 2608541: 2608541
17 CACNA1C NM_000719.6(CACNA1C): c.3387G> A (p.Thr1129=) single nucleotide variant Benign/Likely benign rs188224114 NCBI36 Chromosome 12, 2587968: 2587968
18 CACNA1C NM_000719.6(CACNA1C): c.109G> A (p.Gly37Arg) single nucleotide variant Benign/Likely benign rs34534613 GRCh37 Chromosome 12, 2224449: 2224449
19 CACNA1C NM_000719.6(CACNA1C): c.109G> A (p.Gly37Arg) single nucleotide variant Benign/Likely benign rs34534613 GRCh38 Chromosome 12, 2115283: 2115283
20 CACNA1C NM_000719.6(CACNA1C): c.2436C> T (p.Asp812=) single nucleotide variant Benign rs215976 GRCh37 Chromosome 12, 2694638: 2694638
21 CACNA1C NM_000719.6(CACNA1C): c.2436C> T (p.Asp812=) single nucleotide variant Benign rs215976 GRCh38 Chromosome 12, 2585472: 2585472
22 CACNA1C NM_000719.6(CACNA1C): c.2449C> T (p.Pro817Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs112532048 GRCh37 Chromosome 12, 2694651: 2694651
23 CACNA1C NM_000719.6(CACNA1C): c.2449C> T (p.Pro817Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs112532048 GRCh38 Chromosome 12, 2585485: 2585485
24 CACNA1C NM_000719.6(CACNA1C): c.3642C> T (p.Tyr1214=) single nucleotide variant Conflicting interpretations of pathogenicity rs56394008 GRCh37 Chromosome 12, 2719790: 2719790
25 CACNA1C NM_000719.6(CACNA1C): c.3642C> T (p.Tyr1214=) single nucleotide variant Conflicting interpretations of pathogenicity rs56394008 GRCh38 Chromosome 12, 2610624: 2610624
26 CACNA1C NM_000719.6(CACNA1C): c.3780C> A (p.Gly1260=) single nucleotide variant Conflicting interpretations of pathogenicity rs201258230 GRCh37 Chromosome 12, 2721131: 2721131
27 CACNA1C NM_000719.6(CACNA1C): c.3780C> A (p.Gly1260=) single nucleotide variant Conflicting interpretations of pathogenicity rs201258230 GRCh38 Chromosome 12, 2611965: 2611965
28 CACNA1C NM_000719.6(CACNA1C): c.3786C> T (p.Phe1262=) single nucleotide variant Benign rs216008 GRCh37 Chromosome 12, 2721137: 2721137
29 CACNA1C NM_000719.6(CACNA1C): c.3786C> T (p.Phe1262=) single nucleotide variant Benign rs216008 GRCh38 Chromosome 12, 2611971: 2611971
30 CACNA1C NM_000719.6(CACNA1C): c.4485T> C (p.Asp1495=) single nucleotide variant Benign rs41276710 GRCh37 Chromosome 12, 2774833: 2774833
31 CACNA1C NM_000719.6(CACNA1C): c.4485T> C (p.Asp1495=) single nucleotide variant Benign rs41276710 GRCh38 Chromosome 12, 2665667: 2665667
32 CACNA1C NM_000719.6(CACNA1C): c.5097C> T (p.Ala1699=) single nucleotide variant Benign/Likely benign rs113595214 GRCh37 Chromosome 12, 2788615: 2788615
33 CACNA1C NM_000719.6(CACNA1C): c.5097C> T (p.Ala1699=) single nucleotide variant Benign/Likely benign rs113595214 GRCh38 Chromosome 12, 2679449: 2679449
34 CACNA1C NM_000719.6(CACNA1C): c.5139C> T (p.Asp1713=) single nucleotide variant Benign/Likely benign rs115216455 GRCh37 Chromosome 12, 2788657: 2788657
35 CACNA1C NM_000719.6(CACNA1C): c.5139C> T (p.Asp1713=) single nucleotide variant Benign/Likely benign rs115216455 GRCh38 Chromosome 12, 2679491: 2679491
36 CACNA1C NM_000719.6(CACNA1C): c.5150C> G (p.Ala1717Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs201492706 GRCh37 Chromosome 12, 2788668: 2788668
37 CACNA1C NM_000719.6(CACNA1C): c.5150C> G (p.Ala1717Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs201492706 GRCh38 Chromosome 12, 2679502: 2679502
38 CACNA1C NM_000719.6(CACNA1C): c.522G> A (p.Ala174=) single nucleotide variant Benign rs1544514 GRCh37 Chromosome 12, 2558186: 2558186
39 CACNA1C NM_000719.6(CACNA1C): c.522G> A (p.Ala174=) single nucleotide variant Benign rs1544514 GRCh38 Chromosome 12, 2449020: 2449020
40 CACNA1C NM_000719.6(CACNA1C): c.5361G> A (p.Thr1787=) single nucleotide variant Benign rs1051375 GRCh37 Chromosome 12, 2788879: 2788879
41 CACNA1C NM_000719.6(CACNA1C): c.5361G> A (p.Thr1787=) single nucleotide variant Benign rs1051375 GRCh38 Chromosome 12, 2679713: 2679713
42 CACNA1C NM_000719.6(CACNA1C): c.5451C> T (p.His1817=) single nucleotide variant Likely benign rs113239186 GRCh37 Chromosome 12, 2791722: 2791722
43 CACNA1C NM_000719.6(CACNA1C): c.5451C> T (p.His1817=) single nucleotide variant Likely benign rs113239186 GRCh38 Chromosome 12, 2682556: 2682556
44 CACNA1C NM_000719.6(CACNA1C): c.5604A> G (p.Gln1868=) single nucleotide variant Benign/Likely benign rs11062316 GRCh37 Chromosome 12, 2794932: 2794932
45 CACNA1C NM_000719.6(CACNA1C): c.5604A> G (p.Gln1868=) single nucleotide variant Benign/Likely benign rs11062316 GRCh38 Chromosome 12, 2685766: 2685766
46 CACNA1C NM_000719.6(CACNA1C): c.5649G> A (p.Pro1883=) single nucleotide variant Benign/Likely benign rs56270948 GRCh37 Chromosome 12, 2794977: 2794977
47 CACNA1C NM_000719.6(CACNA1C): c.5649G> A (p.Pro1883=) single nucleotide variant Benign/Likely benign rs56270948 GRCh38 Chromosome 12, 2685811: 2685811
48 CACNA1C NM_000719.6(CACNA1C): c.5665C> T (p.Arg1889Cys) single nucleotide variant Benign/Likely benign rs185788586 GRCh37 Chromosome 12, 2794993: 2794993
49 CACNA1C NM_000719.6(CACNA1C): c.5665C> T (p.Arg1889Cys) single nucleotide variant Benign/Likely benign rs185788586 GRCh38 Chromosome 12, 2685827: 2685827
50 CACNA1C NM_000719.6(CACNA1C): c.5680+11C> T single nucleotide variant Benign/Likely benign rs66611965 GRCh37 Chromosome 12, 2795019: 2795019

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 28)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.08 CACNA1C CACNA2D1 CACNB2 CAMK2G
2
Show member pathways
13.01 CACNA1C CACNA2D1 CACNB2 CAMK2G
3
Show member pathways
12.77 CACNA1C CACNA2D1 CACNB2 CAMK2G
4
Show member pathways
12.71 CACNA2D1 CACNB2 CAMK2G KCNH2 KCNQ1
5
Show member pathways
12.65 CACNA1C CACNA2D1 CACNB2 CAMK2G
6
Show member pathways
12.58 CACNA1C CACNA2D1 CACNB2 CAMK2G
7 12.48 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
12.41 CACNA1C CACNA2D1 CACNB2 CAMK2G KCNE1 KCNQ1
11
Show member pathways
12.3 CACNA1C CACNB2 CAMK2G
12
Show member pathways
12.25 CACNA1C CACNA2D1 CACNB2
13
Show member pathways
12.17 CACNA1C CACNA2D1 CACNB2
14 12.12 CACNA1C CACNB2 KCNE1 KCNH2 KCNQ1
15
Show member pathways
12.03 CACNA1C CACNA2D1 CACNB2 CAMK2G
16
Show member pathways
11.96 CACNA1C CACNA2D1 CACNB2
17 11.85 CACNA1C CACNA2D1 CACNB2
18
Show member pathways
11.8 CACNA1C CACNA2D1 CACNB2
19 11.55 CACNA1C CACNA2D1 CACNB2
20 11.48 CACNA1C CACNA2D1 CACNB2
21 11.39 CACNA1C CACNA2D1 CACNB2 KCNQ1
22 11.35 CACNA1C CACNA2D1 CACNB2
23 11.3 CACNA1C CACNA2D1 CACNB2
24 11.17 CACNA1C CACNB2
25 11.15 CACNA1C CACNA2D1 CACNB2
26 11.1 CACNA1C CACNB2 KCNE1 KCNH2 KCNQ1
27
Show member pathways
10.98 CACNA1C CACNA2D1 CACNB2 CAMK2G KCNE1 KCNQ1
28 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 membrane GO:0016020 9.91 CACNA1C CACNA2D1 CACNB2 CAMK2G KCNE1 KCNH2
2 plasma membrane GO:0005886 9.8 CACNA1C CACNA2D1 CACNB2 CAMK2G KCNE1 KCNH2
3 voltage-gated potassium channel complex GO:0008076 9.33 KCNE1 KCNH2 KCNQ1
4 sarcoplasmic reticulum GO:0016529 9.32 CACNA2D1 CAMK2G
5 voltage-gated calcium channel complex GO:0005891 9.13 CACNA1C CACNA2D1 CACNB2
6 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 29)
# Name GO ID Score Top Affiliating Genes
1 calcium ion transport GO:0006816 9.84 CACNA1C CACNA2D1 CACNB2 CAMK2G
2 ion transport GO:0006811 9.8 CACNA1C CACNA2D1 CACNB2 KCNE1 KCNH2 KCNQ1
3 potassium ion transport GO:0006813 9.78 KCNE1 KCNH2 KCNQ1
4 potassium ion transmembrane transport GO:0071805 9.77 KCNE1 KCNH2 KCNQ1
5 calcium ion transmembrane transport GO:0070588 9.76 CACNA1C CACNA2D1 CACNB2
6 ventricular cardiac muscle cell action potential GO:0086005 9.7 KCNE1 KCNH2 KCNQ1
7 cardiac muscle cell action potential involved in contraction GO:0086002 9.69 CACNA1C CACNA2D1 KCNE1
8 positive regulation of potassium ion transmembrane transport GO:1901381 9.67 KCNE1 KCNH2 KCNQ1
9 potassium ion export across plasma membrane GO:0097623 9.65 KCNE1 KCNH2 KCNQ1
10 cellular response to drug GO:0035690 9.64 KCNH2 KCNQ1
11 cellular response to cAMP GO:0071320 9.64 KCNE1 KCNQ1
12 cardiac muscle contraction GO:0060048 9.63 KCNH2 KCNQ1
13 regulation of calcium ion transport GO:0051924 9.63 CACNA2D1 CAMK2G
14 membrane repolarization during ventricular cardiac muscle cell action potential GO:0098915 9.63 KCNE1 KCNH2 KCNQ1
15 calcium ion import GO:0070509 9.62 CACNA1C CACNB2
16 regulation of potassium ion transmembrane transport GO:1901379 9.62 KCNE1 KCNH2
17 calcium ion transport into cytosol GO:0060402 9.61 CACNA1C CACNA2D1
18 potassium ion export GO:0071435 9.61 KCNE1 KCNH2 KCNQ1
19 regulation of membrane repolarization GO:0060306 9.59 KCNH2 KCNQ1
20 membrane depolarization during AV node cell action potential GO:0086045 9.58 CACNA1C CACNB2
21 membrane repolarization GO:0086009 9.58 KCNE1 KCNH2 KCNQ1
22 positive regulation of high voltage-gated calcium channel activity GO:1901843 9.57 CACNA2D1 CACNB2
23 calcium ion transmembrane transport via high voltage-gated calcium channel GO:0061577 9.56 CACNA1C CACNA2D1
24 membrane depolarization during atrial cardiac muscle cell action potential GO:0098912 9.55 CACNA1C CACNB2
25 membrane repolarization during cardiac muscle cell action potential GO:0086013 9.54 KCNE1 KCNH2 KCNQ1
26 regulation of ventricular cardiac muscle cell membrane repolarization GO:0060307 9.46 CACNA2D1 KCNE1 KCNH2 KCNQ1
27 membrane repolarization during action potential GO:0086011 9.43 KCNE1 KCNH2 KCNQ1
28 regulation of ion transmembrane transport GO:0034765 9.43 CACNA1C CACNA2D1 CACNB2 KCNE1 KCNH2 KCNQ1
29 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 9.67 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 9.48 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
Content
Loading form....