Global Variome shared LOVD
KLKB1 (kallikrein B, plasma (Fletcher factor) 1)
LOVD v.3.0 Build 30b [
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Curator:
Christian Drouet
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The variants shown are described using the NM_000892.3 transcript reference sequence.
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
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
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Operator
Column type
Example
Matches
Text
Arg
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space
Text
Arg Ser
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|
Text
Arg|Ser
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!
Text
!fs
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^
Text
^p.(Arg
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$
Text
Ser)$
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=""
Text
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=""
Text
="p.0"
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!=""
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!=""
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!=""
Text
!="p.0"
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combination
Text
*|Ter !fs
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Date
2020
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|
Date
2020-03|2020-04
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!
Date
!2020-03
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<
Date
<2020
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<=
Date
<=2020-06
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>
Date
>2020-06
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>=
Date
>=2020-06-15
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combination
Date
2019|2020 <2020-03
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Numeric
23
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|
Numeric
23|24
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!
Numeric
!23
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<
Numeric
<23
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<=
Numeric
<=23
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>
Numeric
>23
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>=
Numeric
>=23
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combination
Numeric
>=20 <30 !23
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Some more advanced examples:
Example
Matches
Asian
all entries containing 'Asian', 'asian', including 'Caucasian', 'caucasian', etc.
Asian !Caucasian
all entries containing 'Asian' but not containing 'Caucasian'
Asian|African !Caucasian
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"South Asian"
all entries containing 'South Asian', but not containing 'South East Asian'
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Effect
Exon
DNA change (cDNA)
RNA change
Protein
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
+/.
3_3i
c.143_221+128del
r.?
p.(Gln48Argfs*11)
Both (homozygous)
-
pathogenic (recessive)
g.187153365_187153571del
g.186232211_186232417del
-
-
KLKB1_000011
Nearly asymptomatic parents
Journal: Shahverdi 2017
-
-
Germline
-
-
-
-
-
DNA
SEQ
blood
-
PKKD
-
Journal: Shahverdi 2017
-
F
no
Iran
-
-
-
-
-
1
Christian Drouet
?/.
-
c.337C>T
r.(?)
p.(Arg113Ter)
Unknown
-
VUS
g.187157943C>T
g.186236789C>T
337C>T
-
KLKB1_000007
-
PubMed: Duvvari 2016
-
rs121964949
Germline
-
-
-
-
-
DNA
SEQ, SEQ-NG
-
WES
retinal disease
Pat11AB
PubMed: Duvvari 2016
patient
-
-
Netherlands
white
-
-
-
-
1
LOVD
+/.
5
c.337C>T
r.(?)
p.(Arg113Ter)
Both (homozygous)
-
pathogenic
g.187157943C>T
g.186236789C>T
-
-
KLKB1_000007
Introduced as pathogenic in ClinVar by Dr W Jones, University of Kent and Kent Haemophilia Centre, Canterbury UK
PubMed: Wynne Jones 2004
,
Journal: Jones 2004
ClinVar-VCV000012033.1
rs121964949
Germline
-
0.00006
-
-
-
DNA
SEQ
blood
-
PKKD
patient
PubMed: Wynne Jones 2004
,
Journal: Jones 2004
First description of a kindred with demonstrated homozygous KLKB1 null allele
M
yes
(United Kingdom (Great Britain))
-
-
-
-
-
1
Christian Drouet
+/.
5
c.367G>A
r.(?)
p.(Gly123Arg)
Both (homozygous)
-
pathogenic (recessive)
g.187157973G>A
g.186236819G>A
438G-A (G104R)
-
KLKB1_000010
p.(Gly123Arg) variant in Apple 2 affects the binding function to HMWK
PubMed: Katsuda 2007
,
Journal: Katsuda 2007
ClinVar-VCV000012036.1
rs121964952
Germline
yes
0.000004
-
-
-
DNA
SEQ
blood
-
PKKD
FamPatII7
PubMed: Katsuda 2007
,
Journal: Katsuda 2007
3-generation family, 3 affected (2F, M), unaffected carrier parents/relatives; first cases involving substitutions in the heavy chain of PK which affects blood coagulation
M
yes
Japan
-
-
-
-
-
3
Christian Drouet
-/.
-
c.428=
r.(?)
p.(Ser143=)
Both (homozygous)
-
benign
g.187158034=
g.186236880=
A499G (Asn124Ser)
-
KLKB1_000018
-
PubMed: Katsuda 2007
,
Journal: Katsuda 2007
-
-
Germline
yes
-
-
-
-
DNA
SEQ
blood
-
PKKD
FamPatII7
PubMed: Katsuda 2007
,
Journal: Katsuda 2007
3-generation family, 3 affected (2F, M), unaffected carrier parents/relatives; first cases involving substitutions in the heavy chain of PK which affects blood coagulation
M
yes
Japan
-
-
-
-
-
3
Christian Drouet
-/.
-
c.428G>A
r.(?)
p.(Ser143Asn)
Unknown
-
benign
g.187158034G>A
g.186236880G>A
KLKB1(NM_000892.5):c.428G>A (p.S143N)
-
KLKB1_000001
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-/.
-
c.428G>A
r.(?)
p.(Ser143Asn)
Unknown
-
benign
g.187158034G>A
g.186236880G>A
KLKB1(NM_000892.5):c.428G>A (p.S143N)
-
KLKB1_000001
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-?/-?
5
c.428G>A
r.(?)
p.(Ser143Asn)
Unknown
-
association
g.187158034G>A
g.186236880G>A
-
-
KLKB1_000001
The functional variants KLKB1-c.428G>A and F12-c.-4T>C disrupt the cascade of enzymatic events, resulting in diminished formation of active renin. Combined carriage of both KLKB1-428G/A and F12-46C/T SNPs was associated to an 8.8-year delay in HAE-C1-INH onset and a lower probability to need long term prophylaxis (Gianni 2017)
Journal: Biswas 2016
Journal: Gianni 2017
ClinVar-VCV000012037.9
rs3733402
Germline
-
-
-
-
-
DNA
SEQ
blood
-
Healthy/Control
-
Journal: Biswas 2016
Genotyping 1,180 subjects revealed that the carriers of the F12-c.-4T>C and KLKB1-c.428G>A had a significant association with reduced levels of active plasma renin
-
-
United States
-
-
-
-
-
1180
Christian Drouet
-?/.
5
c.428G>A
r.(?)
p.(Ser143Asn)
Unknown
-
association
g.187158034G>A
g.186236880G>A
-
-
KLKB1_000001
c.428G/A carriers exhibit a significant delayed disease onset by 4.1y depending on the zygocity status: 3.3y for heterozygotes, 4.3y for homozygotes; p.(Ser143Asn) is supposed to disrupt kallikrein-kinin system activation: Ser143 locates in Apple 2 domain, heavy chain, where PK binds to HMWK; Ser to Asn transition results in reduced formation of the PK-HMWK complex, interferences with optimal PK activation and reduction in bradykinin formation and plasma PKa protection from control by C1-INH
Journal: Gianni 2017
Journal: Parsopoulou 2022
ClinVar-VCV000012037.9
rs3733402
Germline
-
0.459793 (GnomAD)
-
-
-
DNA
SEQ
blood
-
HAE1;HAE2
-
Journal: Gianni 2017
C1-INH-HAE patients have been included (n=249), for investigation of c.428G>A SNP association with clinical descriptors of HAE severity
-
-
-
-
-
-
-
-
185
Christian Drouet
+/.
5
c.451dup
r.(?)
p.(Ser151Phefs*34)
Both (homozygous)
-
pathogenic
g.187158057dup
g.186236903dup
-
-
KLKB1_000012
c.451dup is a common polymorphism in Africans (allele frequency 1.12-1.78%), but absent in the European collective.
PubMed: Barco 2020
,
Journal: Barco 2020
,
Journal: Adenaeuer 2021
-
rs560588447
Germline
-
-
-
-
-
DNA
SEQ
-
-
PKKD
-
PubMed: Barco 2020
,
Journal: Barco 2020
-
F
-
Ghana
-
-
-
-
-
1
Christian Drouet
+/.
5
c.451dup
r.(?)
p.(Ser151Phefs*34)
Both (homozygous)
-
pathogenic
g.187158057dup
g.186236903dup
451dupT
-
KLKB1_000012
Proband also carrying functional SNP F12-c.-4C>T and VUS F12-c.413C>A c.451dup is a common polymorphism in Africans (allele frequency 1.12-1.78%), but absent in the European collective.
PubMed: Barco 2020
,
Journal: Barco 2020
-
rs560588447
Germline
-
-
-
-
-
DNA
SEQ
blood
-
PKKD
-
PubMed: Barco 2020
,
Journal: Barco 2020
-
M
-
Somalia
-
-
-
-
-
1
Christian Drouet
+/.
5
c.451dup
r.(?)
p.(Ser151Phefs*34)
Both (homozygous)
-
pathogenic (recessive)
g.187158057dup
g.186236903dup
p.Ser132PhefsTer173
-
KLKB1_000012
Homozygote c.[451dup(;)451dup] Blood coagulation testing presenting with a prolonged aPTT and no immunoreactive prekallikrein detected in the plasma by western blot. All other coagulation factors found in the normal range, including factor XII.
Journal: Dasgupta 2020
-
rs560588447
Germline
-
-
-
-
-
DNA
SEQ
blood
-
PKKD
-
Journal: Dasgupta 2020
-
M
-
United States
-
-
-
-
-
1
Christian Drouet
-?/.
5
c.451dup
r.(?)
p.(Ser151Phefs*34)
Paternal (confirmed)
-
VUS
g.187158057dup
g.186236903dup
-
-
KLKB1_000012
Compound heterozygote c.[451dup];[1643G>A] c.451dup is a common polymorphism in Africans (allele frequency 1.12-1.78%), but absent in the European collective.
{
PubMed: Maak 2009
,
Journal: Maak 2009
,
Journal: Adenaeuer 2021
-
rs560588447
Germline
yes
-
-
-
-
DNA
SEQ
blood
-
PKKD
patient
PubMed: Maak 2009
,
Journal: Maak 2009
2-generation family, 2 affected brothers, unaffected heterozygous parents
M
no
Switzerland
-
-
-
-
-
2
Christian Drouet
+/.
5
c.451dup
r.(?)
p.(Ser151Phefs*34)
Both (homozygous)
-
pathogenic (recessive)
g.187158057dup
g.186236903dup
444_445insT (p.Ser151PhefsTer34) g.186236896_186236897insT
-
KLKB1_000012
Homozygote c.[451dup];[451dup]
PubMed: Abraham 2022
,
Journal: Abraham 2022
-
rs560588447
Germline
-
-
-
-
-
DNA
SEQ-NG-I
blood
-
PKKD
patient
PubMed: Abraham 2022
,
Journal: Abraham 2022
-
M
no
India
-
-
-
-
-
1
Christian Drouet
?/.
-
c.461C>T
r.(?)
p.(Thr154Met)
Unknown
-
VUS
g.187158067C>T
-
KLKB1(NM_000892.3):c.461C>T (p.T154M)
-
KLKB1_000006
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-?/.
-
c.519A>G
r.(?)
p.(=)
Unknown
-
likely benign
g.187159440A>G
-
KLKB1(NM_000892.5):c.519A>G (p.(Gly173=))
-
KLKB1_000021
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+?/+?
7
c.689T>A
r.(?)
p.(Ile230Asn)
Unknown
-
likely pathogenic
g.187171487T>A
g.186250333T>A
-
-
KLKB1_000008
Heterozygous c.689T>A variant is combined with NM_001308.3(CPN1):c.[533G>A;533G>A]
Journal: Vincent 2024
-
rs142420360
Germline
yes
0.000179 (GnomAD_exome); 0.000181 (ExAC); 0.000231 (TOPMED)
-
-
-
DNA
SEQ-NG-IT
blood
-
CPN1D
-
Journal: Vincent 2024
A French family with compound heterozygous female proband has been shown as presenting a carboxypeptidase N deficiency with a decreased circulating kallikrein activity.
F
no
France
-
-
-
-
-
3
Christian Drouet
+?/.
7
c.689T>A
r.(?)
p.(Ile230Asn)
Parent #1
-
likely pathogenic (recessive)
g.187171487T>A
g.186250333T>A
-
-
KLKB1_000008
Compound heterozygous PK deficiency c.[689T>A];[1643G>A]
PubMed: Barco 2020
,
Journal: Barco 2020
-
rs142420360
Germline
-
-
-
-
-
DNA
SEQ
blood
-
PKKD
Pat8
PubMed: Barco 2020
,
Journal: Barco 2020
-
M
-
Germany
-
-
-
-
-
1
Christian Drouet
-/.
-
c.759-12dup
r.(=)
p.(=)
Unknown
-
benign
g.187172361dup
g.186251207dup
KLKB1(NM_000892.5):c.759-12dupT
-
KLKB1_000002
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-/.
7i
c.759-12dup
r.(?)
p.(=)
Parent #2
-
likely benign
g.187172361dup
g.186251207dup
759-12dupT
-
KLKB1_000013
Compound heterozygote c.[759-12dupT](;)[1731T>G] identified prekallikrein Cordoba c.759-12dupT is established as a common polymorphism
Journal: Girolami 2010
-
rs3214676
Germline
-
-
-
-
-
DNA
SEQ
blood
-
PKKD
-
Journal: Girolami 2010
-
M
no
Argentina
Italian background
-
-
-
-
4
Christian Drouet
+/.
11
c.1198G>T
r.(?)
p.(Gly400*)
Parent #1
-
pathogenic (recessive)
g.187173224G>T
g.186252070G>T
-
-
KLKB1_000020
Compound heterozygous PK deficiency c.[1198G>T];[1259G>A]
PubMed: Ryu 2019
,
Journal: Ryu 2019
-
-
Germline
-
-
-
-
-
DNA
SEQ
blood
-
PKKD
patient
PubMed: Ryu 2019
,
Journal: Ryu 2019
-
M
-
Korea
-
-
-
-
-
1
Christian Drouet
+/.
11
c.1204_1205del
r.(?)
p.(Trp402Alafs*35)
Unknown
-
likely pathogenic
g.187173230_187173231del
g.186252076_186252077del
1203_1204del
-
KLKB1_000016
-
PubMed: Barco 2020
,
Journal: Barco 2020
-
rs768319200
Germline
yes
0.000136
-
-
-
DNA
SEQ
blood
-
PKKD
-
PubMed: Barco 2020
,
Journal: Barco 2020
No personal or familial history of bleeding or thrombotic events Variant also found on daughter's and son's samples
M
no
Switzerland
-
-
-
-
-
3
Christian Drouet
+?/.
11
c.1205G>A
r.(?)
p.(Trp402*)
Parent #1
-
likely pathogenic (recessive)
g.187173231G>A
g.186252077G>A
-
-
KLKB1_000017
Compound heterozygous PK deficiency c.[1205G>A];[1643G>A]
PubMed: Barco 2020
,
Journal: Barco 2020
-
rs121964950
Germline
?
0.000004
-
-
-
DNA
SEQ
blood
-
PKKD
-
PubMed: Barco 2020
,
Journal: Barco 2020
-
M
-
Somalia
-
-
-
-
-
1
Christian Drouet
+/.
-
c.1205G>A
r.(?)
p.(Trp402*)
Paternal (confirmed)
-
pathogenic (recessive)
g.187173231G>A
g.186252077G>A
G1298A (Trp383stop)
-
KLKB1_000017
-
PubMed: Lombardi 2003
,
Journal: Lombardi 2003
-
-
Germline
-
-
-
-
-
DNA
SEQ
-
-
PKKD
patient
PubMed: Lombardi 2003
,
Journal: Lombardi 2003
2-generation family, 1 affected, carrier parents slightly low prekallikrein level
M
no
Italy
-
-
-
-
-
1
Johan den Dunnen
+?/.
11
c.1259G>A
r.(?)
p.(Gly420Glu)
Both (homozygous)
ACMG
pathogenic
g.187173285G>A
g.186252131G>A
1352G>A;p.Gly401Glu
-
KLKB1_000009
Gly420 is a conserved residue among mammals. Because of Gly420 (immature protein) is located in the close vicinity of Cys419 (disulfide bridge 419-435) and His434 (catalytic site), it has been hypothesized that the variant product p.(Gly420Glu) may loss the enzyme activity
PubMed: Shigekiyo 2003
,
Journal: Shigekiyo 2003
ClinVar-VCV000225400.1
rs186254196
Germline
yes
0.00001
-
-
-
DNA
SEQ
blood
-
PKKD
FamPatIV1/5
PubMed: Shigekiyo 2003
,
Journal: Shigekiyo 2003
5-generation family, affected brother/sister, unaffected heterozygous carrier parents/relatives
M
yes
Japan
-
-
-
-
-
2
Christian Drouet
+/.
11
c.1259G>A
r.(?)
p.(Gly420Glu)
Parent #2
-
pathogenic (recessive)
g.187173285G>A
g.186252131G>A
-
-
KLKB1_000009
Compound heterozygous PK deficiency c.[1259G>A];[1198G>T]
PubMed: Ryu 2019
,
Journal: Ryu 2019
-
-
Germline
-
-
-
-
-
DNA
SEQ
blood
-
PKKD
patient
PubMed: Ryu 2019
,
Journal: Ryu 2019
-
M
-
Korea
-
-
-
-
-
1
Christian Drouet
-/.
-
c.1314-20T>A
r.(=)
p.(=)
Unknown
-
benign
g.187175722T>A
g.186254568T>A
KLKB1(NM_000892.5):c.1314-20T>A
-
KLKB1_000003
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+?/.
14
c.1643G>A
r.(?)
p.(Cys548Tyr)
Both (homozygous)
-
pathogenic (recessive)
g.187178437G>A
g.186257283G>A
-
-
KLKB1_000014
-
PubMed: Barco 2020
,
Journal: Barco 2020
-
rs121964951
Germline
-
-
-
-
-
DNA
SEQ
blood
-
PKKD
Pat22
PubMed: Barco 2020
,
Journal: Barco 2020
-
M
no
Germany
-
-
-
-
-
1
Christian Drouet
+?/.
14
c.1643G>A
r.(?)
p.(Cys548Tyr)
Parent #2
-
likely pathogenic (recessive)
g.187178437G>A
g.186257283G>A
-
-
KLKB1_000014
Compound heterozygous carrier of c.[c.689T>A];[1643G>A] variants is affected
PubMed: Barco 2020
,
Journal: Barco 2020
ClinVar-SCV002762672.1
rs121964951
Germline
-
0.00068
-
-
-
DNA
SEQ
blood
-
PKKD
Pat8
PubMed: Barco 2020
,
Journal: Barco 2020
-
M
-
Germany
-
-
-
-
-
1
Christian Drouet
+?/.
14
c.1643G>A
r.(?)
p.(Cys548Tyr)
Maternal (confirmed)
-
likely pathogenic (recessive)
g.187178437G>A
g.186257283G>A
-
-
KLKB1_000014
Compound heterozygote c.[451dup];[1643G>A]
PubMed: Maak 2009
,
Journal: Maak 2009
ClinVar-SCV002762672.1
rs121964951
Germline
yes
0.00068
-
-
-
DNA
SEQ
blood
-
PKKD
patient
PubMed: Maak 2009
,
Journal: Maak 2009
2-generation family, 2 affected brothers, unaffected heterozygous parents
M
no
Switzerland
-
-
-
-
-
2
Christian Drouet
+/.
14
c.1643G>A
r.(?)
p.(Cys548Tyr)
Both (homozygous)
-
pathogenic (recessive)
g.187178437G>A
g.186257283G>A
-
-
KLKB1_000014
Homozygote c.[1643G>A];[1643G>A]
PubMed: Dasanu 2009
,
Journal: Dasanu 2009
ClinVar-SCV002762672.1
rs121964951
Germline
-
0.00068
-
-
-
DNA
SEQ
blood
-
PKKD
-
PubMed: Dasanu 2009
,
Journal: Dasanu 2009
-
F
-
Jamaica
-
-
-
-
-
1
Christian Drouet
+/.
14
c.1643G>A
r.(?)
p.(Cys548Tyr)
Both (homozygous)
-
likely pathogenic (recessive)
g.187178437G>A
g.186257283G>A
p.Cys529Tyr
-
KLKB1_000014
Homozygote c.[1643G>A];[1643G>A]
PubMed: Francois 2009
,
Journal: Francois 2007
ClinVar-SCV002762672.1
rs121964951
Germline
-
0.000685
-
-
-
DNA
SEQ
-
-
PKKD
-
PubMed: Francois 2009
,
Journal: Francois 2007
-
F
no
France
-
-
-
-
-
1
Christian Drouet
+?/.
14
c.1643G>A
r.(?)
p.(Cys548Tyr)
Parent #2
-
likely pathogenic (recessive)
g.187178437G>A
g.186257283G>A
-
-
KLKB1_000014
Compound heterozygous PK deficiency c.[1205G>A];[1643G>A]
PubMed: Barco 2020
,
Journal: Barco 2020
ClinVar-SCV002762672.1
rs121964951
Germline
?
0.000685
-
-
-
DNA
SEQ
blood
-
PKKD
-
PubMed: Barco 2020
,
Journal: Barco 2020
-
M
-
Somalia
-
-
-
-
-
1
Christian Drouet
+?/.
-
c.1643G>A
r.(?)
p.(Cys548Tyr)
Maternal (confirmed)
-
likely pathogenic (recessive)
g.187178437G>A
g.186257283G>A
G1736A (Cys529Tyr)
-
KLKB1_000014
-
PubMed: Lombardi 2003
,
Journal: Lombardi 2003
-
-
Germline
-
-
-
-
-
DNA
SEQ
-
-
PKKD
patient
PubMed: Lombardi 2003
,
Journal: Lombardi 2003
2-generation family, 1 affected, carrier parents slightly low prekallikrein level
M
no
Italy
-
-
-
-
-
1
Johan den Dunnen
-/.
-
c.1679G>A
r.(?)
p.(Arg560Gln)
Unknown
-
benign
g.187178473G>A
g.186257319G>A
KLKB1(NM_000892.5):c.1679G>A (p.R560Q)
-
KLKB1_000004
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+/.
15
c.1731T>G
r.(?)
p.(Asp577Glu)
Parent #1
ACMG
VUS
g.187179180T>G
g.186258026T>G
-
-
KLKB1_000015
Compound heterozygote c.[759-12dupT](;)[1731T>G], identified prekallikrein Cordoba c.759-12dupT is established as a common polymorphism
Journal: Girolami 2010
-
-
Germline
-
-
-
-
-
DNA
SEQ
blood
-
PKKD
-
Journal: Girolami 2010
-
M
no
Argentina
Italian background
-
-
-
-
4
Christian Drouet
-/.
15
c.1761=
r.(?)
p.(=)
Both (homozygous)
-
benign
g.187179210=
g.186258056=
C1761T
-
KLKB1_000019
-
PubMed: Katsuda 2007
,
Journal: Katsuda 2007
-
rs925453
Germline
-
-
-
-
-
DNA
SEQ
blood
-
PKKD
FamPatII7
PubMed: Katsuda 2007
,
Journal: Katsuda 2007
3-generation family, 3 affected (2F, M), unaffected carrier parents/relatives; first cases involving substitutions in the heavy chain of PK which affects blood coagulation
M
yes
Japan
-
-
-
-
-
3
Christian Drouet
-/.
-
c.1761T>C
r.(?)
p.(Asn587=)
Unknown
-
benign
g.187179210T>C
g.186258056T>C
KLKB1(NM_000892.5):c.1761T>C (p.N587=)
-
KLKB1_000005
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
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