Legend
Please note that a short description of a certain column can be displayed when you move your mouse cursor over the column's header and hold it still. Below, a more detailed description is shown per column.
Effect : The variant's effect on the function of the gene/protein, displayed in the format 'R/C'. R is the value reported by the source (publication, submitter) and this classification may vary between records. C is the value concluded by the curator. Note that in some database the curator uses Summary records to give details on the classification of the variant.Values used: '+' indicating the variant affects function, '+?' probably affects function, '-' does not affect function, '-?' probably does not affect function, '?' effect unknown, '.' effect was not classified.
Exon : number of exon/intron containing variant; 2 = exon 2, 12i = intron 12, 2i_7i = from intron 2 to intron 7, 8i_9 = intron 8/exon 9 boundary, _1 = 5' to exon 1, 18_ = 3' of exon 18, _1_18_ = encompassing the entire 18-exon gene
DNA change (cDNA) : description of variant at DNA level, based on a coding DNA reference sequence (following HGVS recommendations); e.g. c.123C>T, c.123_145del, c.123_126dup. For deletions/duplications extending beyond the reference transcript resp. {0}/{2} is used to replace del/dup. Extent of the deletion/duplication should be specified using the genomic description (g.). "-" indicates the variant described on genomic level does not affect the coding DNA reference sequence.
RNA change : description of variant at RNA level (following HGVS recommendations).
r.123c>u
r.? = unknown
r.(?) = RNA not analysed but probably transcribed copy of DNA variant
r.spl? = RNA not analysed but variant probably affects splicing
r.(spl?) = RNA not analysed but variant may affect splicing
r.0? = change expected to abolish transcription
Protein : description of variant at protein level (following HGVS recommendations).
p.(Arg345Pro) = change predicted from DNA (RNA not analysed)
p.Arg345Pro = change derived from RNA analysis
p.? = unknown effect
p.0? = probably no protein produced
P-domain : region/domain protein affected
Predict-BioInf : predicted effect of variant using bioinformatic analysis tools (e.g. AGVGD, CADD, conservation, Grantham, MutationTaster, PolyPhen, REVEL, SIFT, splicing, etc.)
Allele : On which allele is the variant located? Does not necessarily imply inheritance! 'Paternal' (confirmed or inferred), 'Maternal' (confirmed or inferred), 'Parent #1' or #2 for compound heterozygosity without having screened the parents, 'Unknown' for heterozygosity without having screened the parents, 'Both' for homozygozity.
Classification method : The method used for the clinical classification of this variant.
All options:
ACMG
ACGS
EAHAD-CFDB
ENIGMA
IARC
InSiGHT
kConFab
other
Clinical classification : Clinical classification of variant, preferably based on standardised criteria (e.g. ACMG), directed on the clinical consequences as published/submitted, indicated using an enriched system including inheritance: e.g. pathogenic, pathogenic (dominant), pathogenic (recessive), pathogenic (!), pathogenic (maternal), pathogenic (paternal). Standard inheritance is covered by dominant/recessive, imprinting by maternal/paternal. A '!' warns for exceptional circumstances to be explained in the 'Remarks' field (low penetrance, variants pathogenic in heterozygous state only, hypomorphic/hypermorphic variants, protective variants, etc.). Non-disease consequences (e.g. drug metabolism (pharmacogenetics), risk factor, blood group, tasting bitter) are indicated using additions to the benign classification; benign (dominant), benign (recessive), benign (!), etc. The value 'association' is used for variants associated with a phenotype and 'NA' for variants from in vitro/in silico records. NOTE: classification may differ from the opinion of the curator as given in a variant SUMMARY-record or the 'Functional effect concluded'). NOTE: pathogenic/likely pathogenic should go together with "variant (probably) affects function" In ClassFunctional.
All options:
pathogenic
pathogenic (dominant)
pathogenic (recessive)
pathogenic (!)
pathogenic (maternal)
pathogenic (paternal)
likely pathogenic
likely pathogenic (dominant)
likely pathogenic (recessive)
likely pathogenic (!)
likely pathogenic (maternal)
likely pathogenic (paternal)
VUS
VUS (!)
likely benign
likely benign (dominant)
likely benign (recessive)
likely benign (!)
likely benign (maternal)
likely benign (paternal)
benign
benign (dominant)
benign (recessive)
benign (!)
benign (maternal)
benign (paternal)
conflicting
association
NA
DNA change (genomic) (hg19) : HGVS description of variant at DNA level, based on the genomic (chromosomal) DNA reference sequence; e.g. g.12345678C>T, g.12345679del, g.12345678_12345890dup
DNA change (hg38) : HGVS description of variant at DNA level, based on the hg38 genomic (chromosomal) eference sequence; e.g. g.12345678C>T, g.12345679del, g.12345678_12345890dup
Published as : listed only when different from "DNA change"; variant as reported originally (e.g. 521delT). Variants seen in animal models, tested in vitro, predicted from RNA analysis, etc. are described between brackets like c.(456C>G)
ISCN : description of the variant according to ISCN nomenclature
DB-ID : database ID of variant, grouping multiple observations of the same variant together, starting with the HGNC gene symbol, followed by an underscore (_) and a six digit number (e.g. DMD_012345). _000000 is used for variants where DNA was not analysed (change predicted from RNA analysis), variants seen in animal models or variants not seen in humans but functionally tested in vitro
Variant remarks : remarks regarding variant described, e.g. germline mosaicism in mother, 345 kb deletion, muscle RNA analysed, not in 200 control chromosomes tested, on founder haplotype, etc.
Reference : publication describing the variant submitted, incl. links to OMIM, PubMed or other source, e.g. "den Dunnen ASHG2003 P2346"
ClinVar ID : ID of variant in ClinVar database
dbSNP ID : the dbSNP ID
Origin : Origin of variant/record: Germline = in all cells, De novo = in all cells, but not in either parent, Germline/De novo (untested) = in all cells, parents not tested (use only when De novo is likely, e.g. isolated/sporadic cases with dominant disease), Somatic = present in a subset of cells, but not in either parent, Uniparental disomy = from parental disomy (maternal or paternal), CLASSIFICATION record = submitter only sharing variant classification (note another report may share Individual data), SUMMARY record = master summary record from curator (may link to another database), In vitro (cloned) = data resulting from in vitro functional assays, animal model = data from animal model, Artefact = false positive variant call, DUPLICATE record = variant already described on another chromosome (e.g. unbalanced translocation, duplicating transposition, 2nd fusion transcript, etc.)
All options:
Germline
De novo
Germline/De novo (untested)
Somatic
Uniparental disomy
Uniparental disomy, maternal allele
Uniparental disomy, paternal allele
CLASSIFICATION record
SUMMARY record
In vitro (cloned)
In silico
animal model
Artefact
DUPLICATE record
Unknown
Not applicable
Segregation : Indicates whether the variant segregates with the phenotype (yes), does not segregate with the phenotype (no) or segregation is unknown (?)
All options:
? = unknown
yes = segregates with phenotype
no = does not segregate with phenotype
- = not applicable
Frequency : frequency in which the variant was found; e.g 5/760 chromosomes (in 5 of 760 chromosomes tested), 1/33 patients (in 1 of 33 patients analysed in study), 0.05 controls (in 5% of control cases tested)
Re-site : restriction enzyme recognition site created (+) or destroyed (-); e.g. BglII+;BamHI-
VIP : variant VIP-status was requested for matchmaking - need collaboration(s) to crack the case - please contact the submitter/curator.
NOTE: to get VIP status ask the curator.
Methylation : result of methylation test; GOM (gain of methylation), LOM (loss of methylation), 30% (30% methylated). NOTE: when several tests were done mention the method as well (e.g. MS-PCR 75%)
Template : Template(s) used to detect the sequence variant; DNA (genomic DNA), RNA (cDNA) or protein
All options:
DNA
RNA = RNA (cDNA)
protein
? = unknown
Technique : technique(s) used to identify the sequence variant.
All options:
? = unknown
ARMS = amplification refractory mutation system
arrayCGH = array for Comparative Genomic Hybridisation
arrayMET = array for methylation analysis
arraySEQ = array for resequencing
arraySNP = array for SNP typing
arrayCNV = array for Copy Number Variation (SNP and CNV probes)
ASO = allele-specific oligo hybridisation
BESS = Base Excision Sequence Scanning
CMC = Chemical Mismatch Cleavage
COBRA = Combined Bisulfite Restriction Analysis
CSCE = Conformation Sensitive Capillary Electrophoresis
CSGE = Conformation Sensitive Gel Electrophoresis
ddF = dideoxy Fingerprinting
DGGE = Denaturing-Gradient Gel-Electrophoresis
DHPLC = Denaturing High-Performance Liquid Chromatography
DOVAM = Detection Of Virtually All Mutations (SSCA variant)
DSCA = Double-Strand DNA Conformation Analysis
DSDI = Detection Small Deletions and Insertions
EMC = Enzymatic Mismatch Cleavage
expr = expression analysis
FISH = Fluorescent In-Situ Hybridisation
FISHf = fiberFISH
HD = HeteroDuplex analysis
HPLC = High-Performance Liquid Chromatography
IEF = IsoElectric Focussing
IHC = Immuno-Histo-Chemistry
Invader = Invader assay
MAPH = Multiplex Amplifiable Probe Hybridisation
MAQ = Multiplex Amplicon Quantification
MCA = Melting Curve Analysis, high-resolution (HRMA)
microscope = microscopic analysis (karyotype)
microsat = microsatellite genotyping
minigene = expression minigene construct
MIP = Molecular Inversion Probe amplification
MIPsm = single molecule Molecular Inversion Probe amplification
MLPA = Multiplex Ligation-dependent Probe Amplification
MLPA-ms = Multiplex Ligation-dependent Probe Amplification, methylation specific
MS = mass spectrometry
Northern = Northern blotting
NUC = nuclease digestion (RNAseT1, S1)
OM = optical mapping
PAGE = Poly-Acrylamide Gel-Electrophoresis
PCR = Polymerase Chain Reaction
PCRdd = PCR, digital droplet
PCRdig = PCR + restriction enzyme digestion
PCRh = PCR, haloplex
PCRlr = PCR, long-range
PCRm = PCR, multiplex
PCRms = PCR, methylation sensitive
PCRq = PCR, quantitative (qPCR)
PCRrp = PCR, repeat-primed (RP-PCR)
PCRsqd = PCR, semi-quantitative duplex
PE = primer extension (APEX, SNaPshot)
PEms = primer extension, methylation-sensitive single-nucleotide
PFGE = Pulsed-Field Gel-Electrophoresis (+Southern)
PTT = Protein Truncation Test
RFLP = Restriction Fragment Length Polymorphisms
RT-PCR = Reverse Transcription and PCR
RT-PCRq = Reverse Transcription and PCR, quantitative
SBE = Single Base Extension
SEQ = SEQuencing (Sanger)
SEQb = bisulfite SEQuencing
SEQp = pyroSequencing
SEQms = sequencing, methylation specific
SEQ-ON = next-generation sequencing - Oxford Nanopore
SEQ-NG = next-generation sequencing
SEQ-NG-RNA = next-generation sequencing RNA
SEQ-NG-H = next-generation sequencing - Helicos
SEQ-NG-I = next-generation sequencing - Illumina/Solexa
SEQ-NG-IT = next-generation sequencing - Ion Torrent
SEQ-NG-R = next-generation sequencing - Roche/454
SEQ-NG-S = next-generation sequencing - SOLiD
SEQ-PB = next-generation sequencing - Pacific Biosciences
SNPlex = SNPlex
Southern = Southern blotting
SSCA = Single-Strand DNA Conformation polymorphism Analysis (SSCP)
SSCAf = fluorescent SSCA (SSCP)
STR = Short Tandem Repeat
TaqMan = TaqMan assay
Western = Western blotting
- = not applicable
Tissue : tissue type used for analysis
Remarks : remarks regarding the screening like WGS (whole genome sequencing), WES (whole exome sequencing, gene panel (incl. a list of genes analysed), etc.
ID_report : ID of the individual that can be publically shared, e.g. as listed in a publication
Reference : reference to publication describing the individual/family, possibly giving more phenotypic details than listed in this database entry, incl. link to PubMed or other source, e.g. "den Dunnen ASHG2003 P2346"
Remarks : remarks about the individual
Gender : gender individual
All options:
? = unknown
- = not applicable
F = female
M = male
rF = raised as female
rM = raised as male
Consanguinity : indicates whether the parents are related (consanguineous), not related (non-consanguineous) or whether consanguinity is not known (unknown)
All options:
no = non-consanguineous parents
yes = consanguineous parents
likely = consanguinity likely
? = unknown
- = not applicable
Country : where (country) does the individual live/recently came from. Give additional details (population, specific sub-group) and when parents come from different countries in "Population". Belgium = individual lives in/recently came from Belgium, (France) = reported by laboratory in France, individual's country of origin not sure
All options:
? (unknown)
- (not applicable)
Afghanistan
(Afghanistan)
Albania
(Albania)
Algeria
(Algeria)
American Samoa
(American Samoa)
Andorra
(Andorra)
Angola
(Angola)
Anguilla
(Anguilla)
Antarctica
(Antarctica)
Antigua and Barbuda
(Antigua and Barbuda)
Argentina
(Argentina)
Armenia
(Armenia)
Aruba
(Aruba)
Australia
(Australia)
Austria
(Austria)
Azerbaijan
(Azerbaijan)
Bahamas
(Bahamas)
Bahrain
(Bahrain)
Bangladesh
(Bangladesh)
Barbados
(Barbados)
Belarus
(Belarus)
Belgium
(Belgium)
Belize
(Belize)
Benin
(Benin)
Bermuda
(Bermuda)
Bhutan
(Bhutan)
Bolivia
(Bolivia)
Bosnia and Herzegovina
(Bosnia and Herzegovina)
Botswana
(Botswana)
Bouvet Island
(Bouvet Island)
Brazil
(Brazil)
British Indian Ocean Territory
(British Indian Ocean Territory)
Brunei Darussalam
(Brunei Darussalam)
Bulgaria
(Bulgaria)
Burkina Faso
(Burkina Faso)
Burundi
(Burundi)
Cambodia
(Cambodia)
Cameroon
(Cameroon)
Canada
(Canada)
Cape Verde
(Cape Verde)
Cayman Islands
(Cayman Islands)
Central African Republic
(Central African Republic)
Central Europe
Chad
(Chad)
Chile
(Chile)
China
(China)
Christmas Island
(Christmas Island)
Cocos (Keeling Islands)
(Cocos (Keeling Islands))
Colombia
(Colombia)
Comoros
(Comoros)
Congo
(Congo)
Cook Islands
(Cook Islands)
Costa Rica
(Costa Rica)
Cote D'Ivoire (Ivory Coast)
(Cote D'Ivoire (Ivory Coast))
Croatia (Hrvatska)
(Croatia (Hrvatska))
Cuba
(Cuba)
Cyprus
(Cyprus)
Czech Republic
(Czech Republic)
Denmark
(Denmark)
Djibouti
(Djibouti)
Dominica
(Dominica)
Dominican Republic
(Dominican Republic)
East Timor
(East Timor)
Ecuador
(Ecuador)
Egypt
(Egypt)
El Salvador
(El Salvador)
England
(England)
Equatorial Guinea
(Equatorial Guinea)
Eritrea
(Eritrea)
Estonia
(Estonia)
Ethiopia
(Ethiopia)
Falkland Islands (Malvinas)
(Falkland Islands (Malvinas))
Faroe Islands
(Faroe Islands)
Fiji
(Fiji)
Finland
(Finland)
France
(France)
Gabon
(Gabon)
Gambia
(Gambia)
Georgia
(Georgia)
Germany
(Germany)
Ghana
(Ghana)
Gibraltar
(Gibraltar)
Greece
(Greece)
Greenland
(Greenland)
Grenada
(Grenada)
Guadeloupe
(Guadeloupe)
Guam
(Guam)
Guatemala
(Guatemala)
Guiana, French
(Guiana, French)
Guinea
(Guinea)
Guinea-Bissau
(Guinea-Bissau)
Guyana
(Guyana)
Haiti
(Haiti)
Heard and McDonald Islands
(Heard and McDonald Islands)
Honduras
(Honduras)
Hong Kong
(Hong Kong)
Hungary
(Hungary)
Iceland
(Iceland)
India
(India)
Indonesia
(Indonesia)
Iran
(Iran)
Iraq
(Iraq)
Ireland
(Ireland)
Israel
(Israel)
Italy
(Italy)
Jamaica
(Jamaica)
Japan
(Japan)
Jordan
(Jordan)
Kazakhstan
(Kazakhstan)
Kenya
(Kenya)
Kiribati
(Kiribati)
Korea
(Korea)
Korea, North (People's Republic)
(Korea, North (People's Republic))
Korea, South (Republic)
(Korea, South (Republic))
Kosovo
(Kosovo)
Kuwait
(Kuwait)
Kyrgyzstan (Kyrgyz Republic)
(Kyrgyzstan (Kyrgyz Republic))
Laos
(Laos)
Latvia
(Latvia)
Lebanon
(Lebanon)
Lesotho
(Lesotho)
Liberia
(Liberia)
Libya
(Libya)
Liechtenstein
(Liechtenstein)
Lithuania
(Lithuania)
Luxembourg
(Luxembourg)
Macau
(Macau)
Macedonia
(Macedonia)
Madagascar
(Madagascar)
Malawi
(Malawi)
Malaysia
(Malaysia)
Maldives
(Maldives)
Mali
(Mali)
Mallorca
(Mallorca)
Malta
(Malta)
Marshall Islands
(Marshall Islands)
Martinique
(Martinique)
Mauritania
(Mauritania)
Mauritius
(Mauritius)
Mayotte
(Mayotte)
Mexico
(Mexico)
Micronesia
(Micronesia)
Moldova
(Moldova)
Monaco
(Monaco)
Mongolia
(Mongolia)
Montserrat
(Montserrat)
Morocco
(Morocco)
Mozambique
(Mozambique)
Myanmar
(Myanmar)
Namibia
(Namibia)
Nauru
(Nauru)
Nepal
(Nepal)
Netherlands
(Netherlands)
Netherlands Antilles
(Netherlands Antilles)
Neutral Zone (Saudia Arabia/Iraq)
(Neutral Zone (Saudia Arabia/Iraq))
New Caledonia
(New Caledonia)
New Zealand
(New Zealand)
Nicaragua
(Nicaragua)
Niger
(Niger)
Nigeria
(Nigeria)
Niue
(Niue)
Norfolk Island
(Norfolk Island)
Northern Ireland
(Northern Ireland)
Northern Mariana Islands
(Northern Mariana Islands)
Norway
(Norway)
Oman
(Oman)
Pakistan
(Pakistan)
Palau
(Palau)
Palestine
(Palestine)
Panama
(Panama)
Papua New Guinea
(Papua New Guinea)
Paraguay
(Paraguay)
Peru
(Peru)
Philippines
(Philippines)
Pitcairn
(Pitcairn)
Poland
(Poland)
Polynesia, French
(Polynesia, French)
Portugal
(Portugal)
Puerto Rico
(Puerto Rico)
Qatar
(Qatar)
Reunion
(Reunion)
Romania
(Romania)
Russia
(Russia)
Russian Federation
(Russian Federation)
Rwanda
(Rwanda)
S. Georgia and S. Sandwich Isls.
(S. Georgia and S. Sandwich Isls.)
Saint Kitts and Nevis
(Saint Kitts and Nevis)
Saint Lucia
(Saint Lucia)
Saint Vincent and The Grenadines
(Saint Vincent and The Grenadines)
Samoa
(Samoa)
San Marino
(San Marino)
Sao Tome and Principe
(Sao Tome and Principe)
Saudi Arabia
(Saudi Arabia)
Scotland
(Scotland)
Senegal
(Senegal)
Serbia
(Serbia)
Seychelles
(Seychelles)
Sierra Leone
(Sierra Leone)
Singapore
(Singapore)
Slovakia (Slovak Republic)
(Slovakia (Slovak Republic))
Slovenia
(Slovenia)
Solomon Islands
(Solomon Islands)
Somalia
(Somalia)
South Africa
(South Africa)
Southern Territories, French
(Southern Territories, French)
Soviet Union (former)
(Soviet Union (former))
Spain
(Spain)
Sri Lanka
(Sri Lanka)
St. Helena, Ascension and Tristan da
Cunha
(St. Helena, Ascension and Tristan da
Cunha)
St. Pierre and Miquelon
(St. Pierre and Miquelon)
Sudan
(Sudan)
Sudan, South
(Sudan, South)
Suriname
(Suriname)
Svalbard and Jan Mayen Islands
(Svalbard and Jan Mayen Islands)
Swaziland
(Swaziland)
Sweden
(Sweden)
Switzerland
(Switzerland)
Syria
(Syria)
Taiwan
(Taiwan)
Tajikistan
(Tajikistan)
Tanzania
(Tanzania)
Thailand
(Thailand)
Togo
(Togo)
Tokelau
(Tokelau)
Tonga
(Tonga)
Trinidad and Tobago
(Trinidad and Tobago)
Tunisia
(Tunisia)
Turkey
(Turkey)
Turkmenistan
(Turkmenistan)
Turks and Caicos Islands
(Turks and Caicos Islands)
Tuvalu
(Tuvalu)
Uganda
(Uganda)
Ukraine
(Ukraine)
United Arab Emirates
(United Arab Emirates)
United Kingdom (Great Britain)
(United Kingdom (Great Britain))
United States
(United States)
Uruguay
(Uruguay)
US Minor Outlying Islands
(US Minor Outlying Islands)
Uzbekistan
(Uzbekistan)
Vanuatu
(Vanuatu)
Vatican City State (Holy See)
(Vatican City State (Holy See))
Venezuela
(Venezuela)
Viet Nam
(Viet Nam)
Virgin Islands (British)
(Virgin Islands (British))
Virgin Islands (US)
(Virgin Islands (US))
Wales
(Wales)
Wallis and Futuna Islands
(Wallis and Futuna Islands)
Western Sahara
(Western Sahara)
Yemen
(Yemen)
Yugoslavia
(Yugoslavia)
Zaire
(Zaire)
Zambia
(Zambia)
Zimbabwe
(Zimbabwe)
Population : population the individual (or ancestors) belongs to; e.g. white, gypsy, Jewish-Ashkenazi, Africa-N, Sardinia, etc.
Age at death : age at which the individual deceased (when applicable):
35y = 35 years
>43y = still alive at 43y
04y08m = 4 years and 8 months
00y00m01d12h = 1 day and 12 hours
18y? = around 18 years
30y-40y = between 30 and 40 years
>54y = older than 54
? = unknown
VIP : individual/phenotype VIP-status was requested for matchmaking - need collaboration(s) to crack the case - please contact the submitter/curator.
NOTE: to get VIP status ask the curator.
Data_av : are additional data available upon request: e.g. pedigree (yes/no/?)
Treatment : treatment of patient
Effect
Exon
DNA change (cDNA)
RNA change
Protein
P-domain
Predict-BioInf
Allele
Classification method
Clinical classification
DNA change (genomic) (hg19)
DNA change (hg38)
Published as
ISCN
DB-ID
Variant remarks
Reference
ClinVar ID
dbSNP ID
Origin
Segregation
Frequency
Re-site
VIP
Methylation
Template
Technique
Tissue
Remarks
Disease
ID_report
Reference
Remarks
Gender
Consanguinity
Country
Population
Age at death
VIP
Data_av
Treatment
Panel size
Owner
+/.
-
c.5252_5259+19del r.spl?
p.?
-
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
TSC2(NM_000548.3):c.5252_5259+19delGCCAGCGGGTAGGGAATATGGGGCTCC
-
TSC2_000661
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
-
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc; RNA evidence in a different case; found with TSC1 missense c.1700C>T
PubMed: Hoogeveen-Westerveld, 2011 -
-
Germline
-
-
BanII-, EciI-
-
-
DNA
SEQ
Blood
-
TSC
-
PubMed: Hoogeveen-Westerveld, 2011 patient has TSC1 missense c.1700C>T and TSC2 splice variant c.5252_5259+19del
?
-
-
-
-
-
-
-
1
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.Arg1751_Arg1753delins34
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
-
-
TSC2_000661
abnormal splicing and a TSC1 5'UTR variant c.-16G>A found; cDNA analysed; del of 8bp from ex41 & 19bp of intron 41 resulted in insertion of 101bp of intron 41 into RNA with creation of 34 new codons (derived from intron 41)
unpublished
-
-
Germline
-
-
BanII-, EciI-
-
-
DNA, RNA
SEQ
Blood
-
TSC
-
unpublished
proband has TSC1 5'UTR variant c.-16G>A and TSC2 splice variant c.5252_5259+19del; parents not tested; intron 40 sequence inserted = CTCAGCGGGGTGTGCTGGCTGCCCAAGCTGTGGGGCGGGTGTGTGGGCAGAGCGGTTGCCACGCCTCCCAGACTTACTGCCCAAGCCGCCTCTGCCTTCAG; amino acids inserted = QRGVLAAQAVGRVCGQSGCHASQTYCPSRLCLQ
?
-
-
-
-
-
-
-
1
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
c.5252_5259+19del27
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc; RNA evidence in a different case
PubMed: Dabora, 2001 -
-
Germline
-
-
BanII-, EciI-
-
-
DNA
DHPLC
Blood
-
TSC
BHM302
PubMed: Dabora, 2001 family with more than 2 affected members; this entry represents 1/3 cases reported in the Harvard DB
?
-
-
-
-
-
-
-
3
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
c.5252_5259+19del27
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc; RNA evidence in a different case
PubMed: Hung, 2006 -
-
Germline
-
-
BanII-, EciI-
-
-
DNA
DHPLC
Blood
-
TSC
6
PubMed: Hung, 2006 -
?
-
Taiwan
Taiwanese
-
-
-
-
1
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
c.5252_5259+19del27
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc; RNA evidence in a different case
PubMed: Dabora, 2001 -
-
Germline
-
-
BanII-, EciI-
-
-
DNA
DHPLC
Blood
-
TSC
ONK522
PubMed: Dabora, 2001 small family with 2 affected members
?
-
-
-
-
-
-
-
2
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
c.5252_5259+19del27
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc; RNA evidence in a different case
originally Kwiatkowski database
-
-
Germline
-
-
BanII-, EciI-
-
-
DNA
SEQ
Blood
-
TSC
-
originally Kwiatkowski database
2 patients with clinical diagnosis of TS; one patient is reported to have a FH of TS; this entry represents 2 out of the 3 cases in the Harvard DB; the other case is accounted for in Dabora, 2001
?
-
-
-
-
-
-
-
2
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
5269 del 27bp
-
TSC2_000661
splice variant; deletion of 27 bases (GCCAGCGGgtagggaatatggggctcc) includes part of exon 41 and part of intron 41; RNA evidence in a different case
unpublished
-
-
Germline
-
-
BanII-, EciI-
-
-
DNA
DHPLC
Blood
-
TSC
-
unpublished
-
?
-
-
-
-
-
-
-
1
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
c.5252_5259+19del27
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc; RNA evidence in a different case
PubMed: Sancak, 2005 -
-
Germline
-
-
BanII-, EciI-
-
-
DNA
SEQ
Blood
-
TSC
-
PubMed: Sancak, 2005 diagnosed with definite TSC
?
-
-
-
-
-
-
-
2
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
c.5252_5259+19del27
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc; RNA evidence in a different case
unpublished
-
-
Germline
-
-
BanII-, EciI-
-
-
DNA
SEQ
Blood
-
TSC
-
unpublished
2 different cases; no other information
?
-
-
-
-
-
-
-
2
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
c.5252_5259+19del27
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc from exon 41 into intron 41; RNA evidence in a different case
unpublished
-
-
Germline
-
-
BanII-, EciI-
-
-
DNA
SEQ
Blood
-
TSC
-
unpublished
TS affected index; child of index has multiple TS skin lesions; half-sib and clinically affected child of index tested; the child has the variant but the half-sib does not; parents of index not tested
M
-
-
-
-
-
-
-
2
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Paternal (confirmed)
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
c.5252_5259+19del27, p.Arg175fs
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc including last 8 nts. of exon 41 and first 19 nts. of intron 41; RNA evidence in a different case; complete screen; MLPA kits P124-B1 (TSC1), P046B2 (TSC2) used
unpublished
-
-
Germline
-
-
BanII-, EciI-
-
-
DNA
SEQ, MLPA
Blood
-
TSC
-
unpublished
clinically affected index; affected parent also tested and found to have variant
M
-
-
-
-
-
-
-
2
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
c.5252_5259+19del27
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc including last 8 nts. of exon 41 and first 19 nts. of intron 41; RNA evidence in a different case; complete screen; MLPA kits P124-B1 (TSC1), P046B2 (TSC2) used
unpublished
-
-
Germline
-
-
BanII-, EciI-
-
-
DNA
SEQ, MLPA
Blood
-
TSC
-
unpublished
parents not tested
M
-
-
-
-
-
-
-
1
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
c.5252_IVS40(+19)del27bp
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc from exon 41 into intron 41; reported as predicted disease-associated variant; RNA evidence in other cases; entire TSC1 and TSC2 genes sequenced; deletion test not done
unpublished
-
-
De novo
-
-
BanII-, EciI-
-
-
DNA
SEQ
Blood
-
TSC
-
unpublished
TS affected; both parents reported as unaffected and tested; variant absent in both parents
M
-
-
-
-
-
-
-
1
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
c.5252-IVS40(+19)del27
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc from exon 41 into intron 41; reported as predicted disease-associated variant; RNA evidence in other cases; entire TSC1 and TSC2 genes sequenced; deletion test not done
unpublished
-
-
Germline
-
-
BanII-, EciI-
-
-
DNA
SEQ
Blood
-
TSC
-
unpublished
TS affected
M
-
-
-
-
-
-
-
1
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.5252_5258delins5259+20_5260-2
p.Arg1751_Arg1753delins34
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
5252_5259+19del27
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc from exon 41 into intron 41; cDNA analysed; del 8bp from ex41 & 19bp from intron 41 causes insertion of 100bp 3'of intron 41 into RNA, creating 34 new codons (derived from intron 41)
unpublished
-
-
Germline
-
-
BanII-, EciI-
-
-
DNA, RNA
SEQ
Blood
-
TSC
-
unpublished
the one parent tested does not have the variant
?
-
-
-
-
-
-
-
1
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.5252_5258delins5259+20_5260-2
p.Arg1751_Arg1753delins34
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
5252_5259+19del27
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc from exon 41 into intron 41; cDNA analysed; del 8bp from ex41 & 19bp from intron 41 causes insertion of 100bp 3'of intron 41 into RNA, creating 34 new codons (derived from intron 41)
unpublished
-
-
De novo
-
-
BanII-, EciI-
-
-
DNA
SEQ
Blood
-
TSC
-
unpublished
1 affected in 1 generation; both parents tested and TSC2 c.5252_5259+19del not found; proband has inherited TSC2 c.1946T>C from one of the parents
?
-
-
-
-
-
-
-
2
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Maternal (confirmed)
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
p.Arg1751Hisfs*21
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc from exon 41 into intron 41; donor splice site affected; RNA evidence in a different case
unpublished
-
-
Germline
-
-
BanII-, EciI-
-
-
DNA
DHPLC, SEQ
Blood
-
TSC
-
unpublished
variant is present in affected parent; both grandparents and a relative tested negative; variant is de novo in affected parent
F
-
-
-
-
-
-
-
2
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
p.Arg1751Hisfs*21
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc from exon 41 into intron 41; donor splice site affected; RNA evidence in a different case
unpublished
-
-
De novo
-
-
BanII-, EciI-
-
-
DNA
DHPLC, SEQ
Blood
-
TSC
-
unpublished
both parents tested negative for variant
F
-
-
-
-
-
-
-
1
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Paternal (confirmed)
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
-
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc from exon 41 into intron 41; donor splice site affected; RNA evidence in a different case
unpublished
-
-
Germline
-
-
BanII-, EciI-
-
-
DNA
DHPLC, SEQ
Blood
-
TSC
-
unpublished
2 children have the same variant; a sibling and five members of one of the parent's family tested negative
M
-
-
-
-
-
-
-
3
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
-
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc from exon 41 into intron 41; donor splice site affected; RNA evidence in a different case
unpublished
-
-
De novo
-
-
BanII-, EciI-
-
-
DNA
DHPLC, SEQ
Blood
-
TSC
-
unpublished
prenatally diagnosed cardiac rhabdomyoma; both parents tested and variant absent
?
-
-
-
-
-
-
-
1
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.Arg1751_Arg1753delins34
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
5252-IVS40+19 27 bp deletion
-
TSC2_000661
splice variant; splice product seen in RNA from other cases in the DB; 27bp deletion of GCCAGCGGgtagggaatatggggctcc from exon 41 into intron 41; donor splice site affected
unpublished
-
-
Germline
-
-
BanII-, EciI-
-
-
DNA
SEQ
Blood
-
TSC
-
unpublished
patient with clinical diagnosis of TS; no FH of TS
?
-
-
-
-
-
-
-
1
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
GAP domain
-
Unknown
-
pathogenic
g.2138319_2138345del g.2088318_2088344del
c.5252_5259+19del27, p.Arg1751fs
-
TSC2_000661
splice variant; 27bp deletion of GCCAGCGGgtagggaatatggggctcc; RNA evidence in a different case
PubMed: Overwater 2016 -
-
De novo
-
-
-
-
-
DNA
SEQ
Blood
-
TSC
-
PubMed: Overwater 2016 -
?
-
-
-
-
-
-
-
1
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
-
-
Unknown
-
pathogenic (dominant)
g.2138319_2138345del -
exon 40
-
TSC2_000661
27bp deletion (GCCAGCGGgtagggaatatggggctcc) includes part of exon 41 and part of intron 41; affects splice site
unpublished
-
-
Germline
?
-
-
-
-
DNA
DHPLC, SEQ
Blood
Diagnostic testing
TSC
-
unpublished
affected parent not tested
F
?
-
-
-
-
-
-
1
Rosemary Ekong
+/.
41_41i
c.5252_5259+19del r.spl
p.?
-
-
Unknown
-
pathogenic (dominant)
g.2138319_2138345del -
exon 40
-
TSC2_000661
-
unpublished
-
-
Germline
?
-
-
-
-
DNA
DHPLC, SEQ
Blood
Diagnostic testing
TSC
-
unpublished
No other family member tested
F
?
-
-
-
-
-
-
1
Rosemary Ekong
+/+
41_41i
c.5252_5259+19del r.[5252_5258delins5259+20_5260-2];[=]
p.Arg1751_Arg1753delins34
GAP domain
affects splicing
Unknown
-
pathogenic (dominant)
g.2138319_2138345del g.2088318_2088344del
-
-
TSC2_000661
27bp deletion (GCCAGCGGgtagggaatatggggctcc) includes ex41 and intron 41; 100 nt. of intron 41 inserted (ctcagcggggtgtgctggctgcccaagctgtggggcgggtgtgtgggcagagcggttgccacgcctcccagacttactgcccaagccgcctctgccttca) creating 34 new aa (RNA evidence)
-
-
-
SUMMARY record
-
-
BanII-, EciI-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
