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

 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
|
-?/. |
_1 |
c.-4811A>G |
r.(=) |
p.(=) |
Both (homozygous) |
- |
likely benign |
g.176841339T>C |
g.177414338T>C |
46 C/C, -4811A>G |
- |
F12_000051 |
- |
PubMed: Chou 2022, Journal: Chou 2022 |
- |
rs2545801 |
Germline |
- |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
F12D |
FamI-CT |
PubMed: Chou 2022, Journal: Chou 2022 |
2-generation family, 1 affected, unaffected heterozygous carriers in the family |
F |
no |
Taiwan |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
?/. |
- |
c.-62C>T |
r.(?) |
p.(=) |
Unknown |
- |
VUS |
g.176836590G>A |
g.177409589G>A |
F12(NM_000505.4):c.-62C>T |
- |
F12_000025 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/. |
- |
c.-62C>T |
r.(?) |
p.(=) |
Unknown |
- |
likely benign |
g.176836590G>A |
- |
F12(NM_000505.4):c.-62C>T |
- |
F12_000025 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+/. |
- |
c.-62C>T |
r.(=) |
p.(=) |
Both (homozygous) |
- |
likely pathogenic (recessive) |
g.176836590G>A |
g.177409589G>A |
c.[-62C>T];[-62C>T] |
- |
F12_000025 |
Homozygous carrier of c.-62C>T variant displays a very low FXII activity |
Journal: Demidova 2023 |
ClinVar-VCV000369463.4 |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
? |
blood |
- |
F12D |
- |
Journal: Demidova 2023 |
- |
M |
- |
Russia |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
-?/. |
- |
c.-57G>C |
r.(?) |
p.(=) |
Unknown |
- |
likely benign |
g.176836585C>G |
g.177409584C>G |
F12(NM_000505.4):c.-57G>C |
- |
F12_000024 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/. |
- |
c.-57G>C |
r.(?) |
p.(=) |
Unknown |
- |
likely benign |
g.176836585C>G |
g.177409584C>G |
F12(NM_000505.4):c.-57G>C |
- |
F12_000024 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+/. |
- |
c.-57G>C |
r.(=) |
p.(=) |
Both (homozygous) |
- |
likely pathogenic (recessive) |
g.176836585C>G |
g.177409584C>G |
c.[-57G>C];[-57G>C] |
- |
F12_000024 |
Homozygous proband plasma samples displays a very low FXII activity |
Journal: Demidova 2023 |
ClinVar-VCV000369462.10 |
rs41309132 |
Germline |
no |
0.00220 |
- |
- |
- |
DNA |
SEQ |
blood |
- |
F12D |
- |
Journal: Demidova 2023 |
- |
F |
- |
Russia |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
-/. |
- |
c.-4T>C |
r.(?) |
p.(=) |
Unknown |
- |
benign |
g.176836532A>G |
g.177409531A>G |
F12(NM_000505.4):c.-4T>C |
- |
F12_000010 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/. |
- |
c.-4T>C |
r.(?) |
p.(=) |
Unknown |
- |
likely benign |
g.176836532A>G |
g.177409531A>G |
F12(NM_000505.4):c.-4T>C |
- |
F12_000010 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-/- |
1 |
c.-4T>C |
r.(?) |
p.(=) |
Unknown |
ACMG |
association |
g.176836532A>G |
g.177409531A>G |
‐46C/T |
- |
F12_000010 |
c.-4T>C, also recognised as F12‐46C/T, creates a new up-stream translational start codon, thereby attenuating formation of the authentic FXII protein; the variant, alias Kozak polymorphism, has been shown to modify the course of HAE-C1-INH; variant is overrepresented in a Spanish HAE-FXII cohort and significantly influences the degree of kallikrein-kinin system activation and the clinical severity
c.-4T>C also decreases FXII activity when associated with F12 variants c.-62C>T, c.-57G>C, and strongly with c.1532-1G>A |
PubMed: Corvillo 2020, Journal: Corvillo 2020 Journal: Demidova 2023 |
ClinVar-VCV000001167.14 |
rs1801020 |
Germline |
no |
0.34803 |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
PubMed: Corvillo 2020, Journal: Corvillo 2020 |
analysis disease expression in 39 Spanish HAE-FXII female index patients carrying the c.1032C>A (Thr328Lys) variant within F12 gene |
F |
- |
Spain |
- |
- |
- |
- |
- |
39 |
Christian Drouet |
+/+ |
1 |
c.1A>G |
r.? |
p.(Arg2Tyr) |
Both (homozygous) |
ACMG |
likely pathogenic |
g.176836528T>C |
g.177409536T>C |
c.[1A>G];[1A>G] |
- |
F12_000058 |
Proband homozygous for the c.1A>G variant; his father, mother, sister and son are all heterozygous.
Predicted harmful by SIFT online software. |
Journal: Ji 2023 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
F12D |
- |
Journal: Ji 2023 |
A Chinese pedigree with a homozygous male proband presenting with a congentital Factor XII deficiency |
M |
yes |
China |
- |
- |
- |
- |
- |
6 |
Christian Drouet |
-?/. |
2i |
c.115+6T>G |
r.(=) |
p.(=) |
Unknown |
- |
likely benign |
g.176836041A>C |
g.177409040A>C |
F12(NM_000505.3):c.115+6T>G |
- |
F12_000028 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/. |
2i |
c.116-224T>C |
r.(=) |
p.(=) |
Unknown |
- |
likely benign |
g.176833286A>G |
- |
- |
- |
F12_000071 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+/+ |
3 |
c.181T>C |
r.(?) |
p.(Cys61Arg) |
Unknown |
- |
likely pathogenic |
g.176832997A>G |
g.177406042A>G |
- |
- |
F12_000066 |
- |
Journal: Han 2015 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
F12D |
- |
Journal: Han 2015 |
- |
M |
no |
China |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
?/. |
- |
c.218G>C |
r.(?) |
p.(Cys73Ser) |
Unknown |
- |
VUS |
g.176832804C>G |
- |
F12(NM_000505.3):c.218G>C (p.C73S) |
- |
F12_000034 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+?/. |
4 |
c.218G>C |
r.(?) |
p.(Cys73Ser) |
Unknown |
- |
likely pathogenic |
g.176832804C>G |
- |
F12(NM_000505.3):c.218G>C (p.C73S) |
- |
F12_000034 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
?/. |
4 |
c.223A>G |
r.(?) |
p.(Thr75Ala) |
Unknown |
- |
VUS |
g.176832799T>C |
- |
F12(NM_000505.4):c.223A>G (p.T75A) |
- |
F12_000072 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+?/+? |
5 |
c.346G>A |
r.(?) |
p.(Gly116Ser) |
Paternal (confirmed) |
- |
likely pathogenic (recessive) |
g.176832375C>T |
g.177405374C>T |
c.[346G>A];[1583C>A] |
- |
F12_000063 |
Compound heterozygous variant with c.1583C>A |
Journal: Cheng 2023 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
F12D |
- |
Journal: Cheng 2023 |
- |
- |
- |
China |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
-?/. |
- |
c.348C>A |
r.(?) |
p.(Gly116=) |
Unknown |
- |
likely benign |
g.176832373G>T |
g.177405372G>T |
F12(NM_000505.3):c.348C>A (p.G116=) |
- |
F12_000022 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-/. |
- |
c.398-12C>T |
r.(=) |
p.(=) |
Unknown |
- |
benign |
g.176832198G>A |
g.177405197G>A |
- |
- |
F12_000021 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+?/+? |
6 |
c.405C>A |
r.(?) |
p.(Cys135*) |
Both (homozygous) |
- |
likely pathogenic (recessive) |
g.176832179G>T |
g.177405178G>T |
c.[405C>A];[405C>A] |
- |
F12_000061 |
- |
Journal: Kwon 2010 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
F12D |
- |
Journal: Wong 2010 |
- |
M |
- |
Korea |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
-?/. |
- |
c.418C>G |
r.(?) |
p.(Leu140Val) |
Unknown |
- |
likely benign |
g.176832166G>C |
g.177405165G>C |
F12(NM_000505.3):c.418C>G (p.L140V) |
- |
F12_000020 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/. |
- |
c.418C>G |
r.(?) |
p.(Leu140Val) |
Unknown |
- |
likely benign |
g.176832166G>C |
g.177405165G>C |
F12(NM_000505.3):c.418C>G (p.L140V) |
- |
F12_000020 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/. |
- |
c.418C>G |
r.(?) |
p.(Leu140Val) |
Unknown |
- |
likely benign |
g.176832166G>C |
- |
F12(NM_000505.3):c.418C>G (p.L140V) |
- |
F12_000020 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/. |
6 |
c.418C>G |
r.(?) |
p.(Leu140Val) |
Unknown |
- |
likely benign |
g.176832166G>C |
g.177405165G>C |
- |
- |
F12_000020 |
Conflicting interpretation of pathogenicity
-1. VUS as introduced by GeneDx, Gaithersburg MA
-2. Likely benign as introduced by CeGaT Center for Human Genetics Tübingen, Germany. Criteria applied: BP4, BS1
-3. Benign as introduced by CeMIA, Larissa Greece |
- |
ClinVar-SCV003842612.1 |
rs35515200 |
SUMMARY record |
- |
0.00247 (gnomAD) |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/. |
- |
c.552C>T |
r.(?) |
p.(Leu184=) |
Unknown |
- |
likely benign |
g.176831893G>A |
- |
F12(NM_000505.3):c.552C>T (p.L184=) |
- |
F12_000046 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+/+ |
7 |
c.566G>C |
r.(?) |
p.(Cys189Ser) |
Unknown |
- |
likely pathogenic |
g.176831879C>G |
g.177404878C>G |
- |
- |
F12_000068 |
- |
Journal: Han 2015 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
F12D |
- |
Journal: Han 2015 |
- |
F |
no |
China |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
+/. |
7 |
c.615del |
r.(?) |
p.(Gly206Glufs*45) |
Unknown |
- |
likely pathogenic |
g.176831831del |
g.177404830del |
- |
- |
F12_000055 |
- |
Journal: Demidova 2023 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
? |
blood |
- |
F12D |
- |
Journal: Demidova 2023 |
- |
- |
- |
Russia |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
-?/-? |
7 |
c.619G>C |
r.(?) |
p.(Ala207Pro) |
Both (homozygous) |
- |
VUS |
g.176831826C>G |
g.177404825C>G |
F12(NM_000505.4):c.619G>C (p.A207P) |
- |
F12_000005 |
VKGL data sharing initiative Nederland.
To be noted. Pechnikova 2023 described a 13-year-old girl with symptoms of HAE who is homozygous for the allele encoding FXII-Ala207Pro and speculated that the Pro207 form of FXII may contribute to her symptoms. The patient’s father, who does not exhibit symptoms of HAE, is also homozygous for FXII-Pro207, while her mother is heterozygous for this polymorphism.
Shamanaev 2025 shows that there is no obvious difference between FXII-Ala207 and FXII-Pro207 in their capacities to support reciprocal activation and subsquent KKS devlopment. |
Journal: Pechnikova 2023 Journal: Shamanaev 2025 |
ClinVar-SCV001441476.1 |
rs17876030 |
CLASSIFICATION record |
no |
0.034661 |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-/. |
- |
c.619G>C |
r.(?) |
p.(Ala207Pro) |
Unknown |
- |
benign |
g.176831826C>G |
g.177404825C>G |
F12(NM_000505.4):c.619G>C (p.A207P) |
- |
F12_000005 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/-? |
7 |
c.619G>C |
r.(?) |
p.(Ala207Pro) |
Unknown |
- |
benign |
g.176831826C>G |
g.177404825C>G |
- |
- |
F12_000005 |
- |
Journal: Kiss 2013 |
ClinVar-RCV000264675.9 |
rs17876030 |
Germline |
- |
- |
- |
- |
- |
DNA |
SEQ |
- |
- |
HAE3 |
- |
Journal: Kiss 2013 |
A Hungarian pedigree with 5 affected individuals, 3 female and 2 male |
F |
no |
Hungary |
- |
- |
- |
- |
- |
5 |
Christian Drouet |
-/. |
- |
c.711C>T |
r.(?) |
p.(Pro237=) |
Unknown |
- |
benign |
g.176831589G>A |
g.177404588G>A |
- |
- |
F12_000009 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-/. |
- |
c.711C>T |
r.(=) |
p.(=) |
Parent #1 |
- |
benign |
g.176831589G>A |
g.177404588G>A |
- |
- |
F12_000009 |
15 heterozygous, no homozygous; Clinindb (India) |
PubMed: Narang 2020, Journal: Narang 2020 |
- |
rs17876047 |
Germline |
- |
15/2794 individuals |
- |
- |
- |
DNA |
arraySNP |
- |
Infinium Global Screening Array v1.0 |
? |
- |
PubMed: Narang 2020, Journal: Narang 2020 |
analysis 2794 individuals (India) |
- |
- |
India |
- |
- |
- |
- |
- |
15 |
Mohammed Faruq |
?/. |
8 |
c.721T>G |
r.(?) |
p.(Trp241Gly) |
Parent #2 |
- |
VUS |
g.176831579A>C |
- |
- |
- |
F12_000043 |
- |
Journal: Matsukuma 2011 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
SEQ |
- |
- |
F12D |
- |
Journal: Matsukuma 2011 |
Original single family with a male proband |
M |
no |
Japan |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
-/. |
- |
c.756C>T |
r.(?) |
p.(Ala252=) |
Unknown |
- |
benign |
g.176831544G>A |
g.177404543G>A |
- |
- |
F12_000019 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
?/. |
9 |
c.827G>A |
r.(?) |
p.(Trp276*) |
Paternal (confirmed) |
- |
VUS |
g.176831388C>T |
g.177404387C>T |
- |
- |
F12_000001 |
- |
PubMed: Bosch 2015, Journal: Bosch 2015 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
PCR, SEQ, SEQ-NG |
- |
- |
CVI, ID |
26350515-Pat12 |
PubMed: Bosch 2015, Journal: Bosch 2015, PubMed: Bosch 2016, Journal: Bosch 2016 |
- |
M |
? |
Netherlands |
white |
- |
- |
- |
- |
1 |
Danielle Bosch |
+/. |
- |
c.827G>A |
r.(?) |
p.(Trp276*) |
Unknown |
- |
pathogenic |
g.176831388C>T |
- |
F12(NM_000505.4):c.827G>A (p.W276*) |
- |
F12_000001 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/. |
9 |
c.849C>T |
r.(?) |
p.(Asp283=) |
Unknown |
- |
likely benign |
g.176831366G>A |
g.177404365G>A |
F12(NM_000505.3):c.849C>T (p.D283=) |
- |
F12_000027 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+/+ |
9 |
c.859T>A |
r.(?) |
p.(Trp287Arg) |
Unknown |
- |
pathogenic |
g.176831356A>T |
g.177404359A>T |
- |
- |
F12_000040 |
p.(Trp287Arg) variant affects the kringle domain of factor XII.
Spontaneously active p.(Trp287Arg) variant product in the recombinantly production medium; prone to intracellular autoactivation and accelerating FXII activation and overriding C1-INH control function. |
Journal: Hofman 2020 Journal: Scheffel 2020 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
FCAS1 |
- |
Journal: Hofman 2020 Journal: Scheffel 2020 |
A German family (n=4) presenting with urticarial and autoinflammatory syndrome |
M |
- |
Germany |
- |
- |
- |
- |
- |
4 |
Christian Drouet |
+?/+? |
9 |
c.894_911dup |
r.(?) |
p.(Gln300_Thr305dup) |
Unknown |
ACMG |
pathogenic |
g.176831306_176831323dup |
g.177404305_177404322dup |
c.892_909dup |
- |
F12_000036 |
No functional evidence in the report for this variation.
Incomplete penetrance: 3 symptomatic individuals within 6 carriers of c.894_911dup variant.
In-frame duplication of 6 residues (Gln300_Thr305dup) within the Pro-rich region of the Kringle domain of factor XII.
The c.894_911dup variant has been introduced in ClinVar as pathogenic by the lab of MM Nöthen, Institute of Human Genetics, University Hospital Bonn Germany. |
Journal: Kiss 2013 PubMed: Kiss 2013 |
ClinVar-SCV000502993.2 |
rs774034606 |
Germline |
yes |
1/149302 |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Kiss 2013 |
A Hungarian pedigree with 5 affected individuals, 3 female and 2 male |
F |
no |
Hungary |
- |
- |
- |
- |
- |
5 |
Christian Drouet |
-?/. |
9 |
c.914C>T |
r.(?) |
p.(Thr305Ile) |
Unknown |
- |
likely benign |
g.176831301G>A |
- |
F12(NM_000505.3):c.914C>T (p.T305I) |
- |
F12_000047 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
?/. |
- |
c.922T>A |
r.(?) |
p.(Ser308Thr) |
Unknown |
- |
VUS |
g.176831293A>T |
- |
F12(NM_000505.3):c.922T>A (p.S308T) |
- |
F12_000035 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+/+ |
9_9i |
c.971_1018+24del |
r.? |
p.(Lys324_Ala340delinsThr) |
Unknown |
ACMG |
pathogenic |
g.176831175_176831246del |
g.177404174_177404245del |
- |
- |
F12_000037 |
A Brazilian male carrier is presenting with a HAE phenotype triggered by ACEi intake (Veronez 2018).
The F12 c.971_1018+24del72 variant is predicted to result in an in-frame deletion p.(Lys324_Ala340delinsThr). |
Journal: Bork 2011 Journal: Bork 2014 Journal: Veronez 2017 Journal: Veronez 2018 Journal: Veronez 2021 |
ClinVar-VCV000441533.1 |
rs1554097246 |
Germline |
yes |
0.0001 (ALFA project) |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Bork 2011 Journal: Bork 2014 Journal: Veronez 2018 |
Four independent kindreds have been found as carrying a c.971_1018+24del variant
Families 1 and 2, Germany, Turkish origin, with 4 affected female individuals
Family 3, Brazil (male individual; history of ACEi intake)
Family 4, Brazil (n=2) |
- |
no |
Turkey |
- |
- |
- |
- |
- |
7 |
Christian Drouet |
+/+ |
9_9i |
c.971_1018+24del |
r.? |
p.(Lys324_Ala340delinsThr) |
Unknown |
ACMG |
pathogenic |
g.176831175_176831246del |
g.177404174_177404245del |
- |
- |
F12_000037 |
The F12 c.971_1018+24del72 variant is predicted to result in an in-frame deletion p.(Lys324_Ala340delinsThr). No analysis of transcripts available. |
Journal: Bork 2011 |
ClinVar-VCV000441533.1 |
rs1554097246 |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Bork 2011 |
Single family |
F |
no |
Turkey |
- |
- |
- |
- |
- |
3 |
Christian Drouet |
+/+ |
9_9i |
c.971_1018+24del |
r.? |
p.(Lys324_Ala340delinsThr) |
Unknown |
ACMG |
pathogenic |
g.176831173_176831244del |
g.177404174_177404245del |
- |
- |
F12_000037 |
Two independent Brazilian families have been shown as carrying a g.177404174_177404245del variant.
The F12 c.971_1018+24del variant is predicted to result in an in-frame deletion p.(Lys324_Ala340delinsThr). No analysis of transcripts available. |
Journal: Moreno 2015 Journal: Veronez 2018 Journal: Gabriel 2025 |
ClinVar-SCV005350560.1 |
rs1554097246 |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Veronez 2018 Journal: Veronez 2021 Journal: Gabriel 2025 |
Numerous Brazilian pedigrees have been recorded as carrying a c.1032C>A variant, with 94 families and 176 heterozygous carriers.
Incomplete penetrance demonstrated in a family where 9/19 symptomatic individuals have been recorded.
The course of pregnancies in women diagnosed with HAE-nC1-INH has been described for 7 carriers of a F12 variant. |
- |
no |
Brazil |
- |
- |
- |
- |
- |
176 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
- |
pathogenic |
g.176831232G>T |
g.177404231G>T |
F12(NM_000505.3):c.983C>A (p.T328K), F12(NM_000505.4):c.983C>A (p.T328K) |
- |
F12_000008 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Parent #1 |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
- |
Journal: Charignon 2018 |
ClinVar-000001169 |
rs118204456 |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
- |
- |
HAE1;HAE2 |
FamPatIII1 |
PubMed: Charignon 2018, Journal: Charignon 2018 |
2-generation family, 2 affected (2F) |
F |
no |
France |
- |
- |
- |
- |
- |
3 |
Christian Drouet |
+/. |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
- |
pathogenic |
g.176831232G>T |
g.177404231G>T |
F12(NM_000505.3):c.983C>A (p.T328K), F12(NM_000505.4):c.983C>A (p.T328K) |
- |
F12_000008 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+/. |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
c.1032C>A |
- |
F12_000008 |
Four independent German kindreds have been found as carrying a c.983C>A variant |
Journal: Dewald 2006 |
ClinVar-VCV000001169.8 |
rs118204456 |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Dewald 2006 |
Four independent German kindreds have been found as carrying a c.983C>A variant
Family 1, n=2
Family 2, n=5
Family 3, n=6
Family 4, n=6 |
F |
no |
Germany |
- |
- |
- |
- |
- |
19 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
Numerous Brazilian pedigrees have been recorded as carrying a c.983C>A variant, with 94 families and 176 heterozygous patients.
Incomplete prenetrance: 79 asymptomatic relatives within 180 carriers of a c.983C>A variant.
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Veronez 2018 Journal: Veronez 2021 Journal: Gabriel 2025 |
ClinVar-VCV000001169.8 |
rs118204456 |
Germline |
yes |
0.000004 (GnomAD_exome) |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Veronez 2018 Journal: Veronez 2021 Journal: Gabriel 2025 |
Numerous Brazilian pedigrees have been recorded as carrying a c.1032C>A variant, with 94 families and 176 heterozygous carriers.
Incomplete penetrance demonstrated in a family where 9/19 symptomatic individuals have been recorded.
The course of pregnancies in women diagnosed with HAE-nC1-INH has been described for 7 carriers of a F12 variant. |
- |
no |
Brazil |
- |
- |
- |
- |
- |
176 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Both (homozygous) |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
c.[983C>A];[983C>A] |
- |
F12_000008 |
Two Brazilian pedigrees have been recorded as segregating a c.983 C>A;(p.Thr328Lys) variant, with 1 homozygous carrier, one male and one female, respectively in each family.
Fourteen affected individuals.
Homozygosity for c.983C>A variant lead to develop disease symptoms in males - heterozygous male carriers normally do not develop disease symptoms - and a more severe disease phenotype in females compared to patients heterozygous for the F12 c.983 C>A variant. |
Journal: Grumach 2016 Journal: Stieber 2014 |
ClinVar-VCV000001169.8 |
rs118204456 |
Germline |
yes |
0.000004 (GnomAD_exome) |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Grumach 2016 |
Two Brazilian families are presenting with homozygous carriers of a c.983C>A variant, one male and one female |
- |
- |
Brazil |
- |
- |
- |
- |
- |
14 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
Nine families and 23 affected individuals
Important Italian cohort from that has been assessed a prevalence of 1:1.4 × E6 for HAE-FXII.
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Bova 2020 |
ClinVar-VCV000001169.8 |
rs118204456 |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
- |
Nine independent Italian kindreds have been shown as carrying a c.983C>A variant, with 23/43 affected individuals, 32 females and 11 males |
- |
- |
Italy |
- |
- |
- |
- |
- |
23 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
First Australian case with HAE-FXII.
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Bell 2008 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
- |
Single family |
F |
no |
Australia |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
3 female individuals have been shown as affected.
A single male carrier of c.983C>A variant is shown asymptomatic.
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Prieto 2009 |
ClinVar-VCV000001169.8 |
rs118204456 |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
- |
Single family |
F |
no |
Spain |
- |
- |
- |
- |
- |
3 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Bork 2009 Journal: Bork 2023 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Bork 2009 |
Additional 10 German pedigrees shown as carrying a c.983C>A variant
Female individuals are affected |
F |
no |
Germany |
- |
- |
- |
- |
- |
45 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
c.1032C>A |
- |
F12_000008 |
The first French pedigree affected by HAE-F12.
Incomplete penetrance: 8/13 affected individuals. Haplotype analyses with use of SNPs at the F12 locus provided evidence that the French family and 3 of the German families reported by Dewald and Bork (2006) shared a common founder.
Plasma displays a gain-of-function of kallikrein-kinin system; p.(Thr328Lys) exhibits a lower glycosylation, with subsequent increased autoactivation of zymogen F12.
Thr to Lys transition has consequence on the protein’s folding and conformation, with an open or relaxed conformation facilitating the access of kallikrein and plasmin and exposing cryptic proteolytic targets for thrombin that are normally concealed and not accessible in the compact conformation of FXII.
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod. |
Journal: Martin 2001 Journal: Cichon 2006 Journal: Björkvist 2015 Journal: de Maat 2016 |
ClinVar-VCV000001169.8 |
rs118204456 |
Germline |
yes |
0.000004 (1/234142, GnomAD_exome) |
- |
- |
- |
DNA |
SEQ |
- |
- |
HAE3 |
- |
Journal: Cichon 2006 Journal: Björkvist 2015 Journal: de Maat 2016 |
A French pedigree with 8 affected individuals within 13 carriers of a c.983C>A variant |
- |
- |
France |
- |
- |
- |
- |
- |
8 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
A single Canadian pedigree with 6 affected female individuals.
Affected females have polymorphisms associated with lower levels of both APP and ACE, the major enzymes responsible for bradykinin catabolism. Three patients also carry the A allele of SNP rs3788853 in the XPNPEP2 gene, which may have contributed to the phenotype, making this observation the first one with multiple genes that might contribute to estrogen-dependent or estrogen associated HAE-F12. But this allele is also found in 10 unaffected family members.
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Duan 2009 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
- |
A single Canadian family with 6 symptomatic carriers of a c.983C>A variant |
F |
no |
Canada |
- |
- |
- |
- |
- |
6 |
Christian Drouet |
+/. |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
A single French pedigree with women and man.
C1Inh function drops of 10% to 40% compared to normal in female individuals, in line with the cleavage of the serpin from 105 to 95 kd without development of serpin-protease association, suggesting p.(Met328Lys) beyond the control of C1-INH |
Journal: Martin 2007 |
ClinVar-VCV000001169 |
rs118204456 |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
- |
A French pedigree with affected man (n=1) and women (n=2)
Incomplete penetrance: 3/7 are affected |
- |
no |
France |
- |
- |
- |
- |
- |
3 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
Nine families with 29 affected individuals.
Symptomatic individuals have been found as carriers of a c.-2399C variant of XPNPEP2 gene, and a DD or ID polymporphism of ACE gene. |
Journal: Piñero-Saavedra 2016 |
ClinVar-VCV000001169.8 |
rs118204456 |
Germline/De novo (untested) |
yes |
0.000004 (GnomAD_exome) |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Piñero-Saavedra 2016 |
Prospective Spanish cohort study with 9 families and 24 symptomatic individuals |
- |
no |
Spain |
- |
- |
- |
- |
- |
24 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Moreno 2015 |
ClinVar-VCV000001169.8 |
rs118204456 |
Germline |
yes |
0.000004 (GnomAD_exome) |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Moreno 2015 |
Four Brazilian kindreds have been reported as carrying a c.983C>A variant, with 8/16 affected individuals |
- |
no |
Brazil |
- |
- |
- |
- |
- |
8 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
Four independent kindreds have been found as carrying a c.983C>A variant.
Family 1, n=5 (female)
Family 2, n=7 (female)
Family 3, n=1 (female)
Family 4, n=2 (female)
All carriers also carry the same combined SNPs already described by Cichon 2006, demonstrating a common ancestor.
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Firinu 2015 |
ClinVar-VCV000001170.4 |
rs118204456 |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Firinu 2015 |
Four Sardininan independent kindreds have been found as carrying a c.983C>A variant |
F |
no |
Italy |
Sardinian |
- |
- |
- |
- |
15 |
Christian Drouet |
+/. |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
Thirteen kindreds from North-Western Spain have been found as carrying a c.983C>A variant, with 29 affected individuals |
Journal: Marcos 2012 |
ClinVar-VCV000001169.8 |
rs118204456 |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Marcos 2012 |
Thirteen kindreds from North-West Spain, with 29 affected individuals |
- |
no |
Spain |
- |
- |
- |
- |
- |
29 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Baeza 2011 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Baeza 2011 |
Single family |
F |
no |
Morocco |
- |
- |
- |
- |
- |
3 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
Two families with 5 affected female individuals; 3 are presenting with severe obstetrical complications |
Journal: Picone 2010 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Picone 2010 |
Symptoms and obstetrical complications of women in two families with HAE attributable to the c.983C>A variant in the F12 gene.
Family 1, n=2
Family 2, n=3 |
F |
- |
France |
- |
- |
- |
- |
- |
5 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
A single Italian pedigree with 3 affected female individuals.
The patients also carry the same combination of SNPs already observed in the first description by Cichon et al 2006, demonstrating c983C>A as a common ancestral variant among affected individuals in western Europe.
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Nagy 2009 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Nagy 2009 |
The first British pedigree ever shown as carrying a c.983C>A variant, with 3 affected female individuals |
F |
- |
United Kingdom (Great Britain) |
- |
- |
- |
- |
- |
3 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
A Spanish kindred has been shown as carrying a c.983C>A variant, with 2 affected individuals |
Journal: Veronez 2019 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ-NG |
blood |
- |
HAE3 |
- |
Journal: Veronez 2019 |
Single family |
F |
no |
Spain |
- |
- |
- |
- |
- |
2 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
24 French pedigrees have been shown as carrying a c.983C>A variant, with 37/57 affected individuals.
Family origin: 12/24 from Northern Africa.
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod. |
Journal: Deroux 2016 |
ClinVar-VCV000001169 |
rs118204456 |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Deroux 2016 |
24 French pedigrees have been shown as carrying a c.983C>A variant |
- |
no |
France |
- |
- |
- |
- |
- |
37 |
Christian Drouet |
+/. |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
- |
Journal: Mendoza-Alvarez 2022 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
Fam2 |
Journal: Mendoza-Alvarez 2022 |
3-generation family, 4 affected, father/3 daughters |
F;M |
no |
Spain |
- |
- |
- |
- |
- |
4 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
- |
pathogenic |
g.176831232G>T |
g.177404231G>T |
F12(NM_000505.3):c.983C>A (p.T328K), F12(NM_000505.4):c.983C>A (p.T328K) |
- |
F12_000008 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
Isolated HAE-nC1-INH individuals carrying a c.983C>A variant (10 families): Occurrence of only one symptomatic patient per family, who had no family history of angioedema but who had symptom-free relatives carrying the same HAE-linked c.983C>A variant.
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Bork 2023 |
ClinVar-000001169 |
rs118204456 |
Germline |
yes |
0.00001 |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Bork 2023 |
Ten independent families: 10 isolated HAE-nC1-INH individuals carrying a c.983C>A variant in F12 gene |
- |
no |
Germany |
- |
- |
- |
- |
- |
10 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Hentges 2009 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Hentges 2009 |
Single family with a single female affected individual |
F |
no |
Luxembourg |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Gomez-Traseira 2010 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Gomez-Traseira 2010 |
Single family: Five affected individuals within 11 carriers |
F |
no |
Spain |
- |
- |
- |
- |
- |
5 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Mansi 2015 |
ClinVar-SCV002240385.3 |
rs118204456 |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Mansi 2015 |
Three independent families, 3 affected individuals, presenting with a HAE-F12 phenotype |
- |
no |
Italy |
- |
- |
- |
- |
- |
3 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
- |
Journal: Stieber 2015 |
ClinVar-SCV001441472.1 |
rs118204456 |
Germline |
yes |
0.000004271 |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Stieber 2015 |
First report of a Brazilian family and of 12 affected individuals presenting with a HAE-F12 phenotype |
- |
no |
Brazil |
- |
- |
- |
- |
- |
12 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Bork 2017 |
- |
rs118204456 |
Germline |
yes |
0.000004 |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Bork 2017 |
One family with 4 affected individuals |
- |
no |
Germany |
- |
- |
- |
- |
- |
4 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
- |
Journal: Lochbaum 2023 |
- |
rs118204456 |
Germline |
- |
0.000004 |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Lochbaum 2023 |
Clinical presentation: abdominal edema and edema of the limbs under estrogen intake |
F |
no |
Germany |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
Clinical presentation: Recurrent edema of the limbs, lips, face, abdomen, lasting approx. five days.
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Lochbaum 2023 |
- |
rs118204456 |
Germline |
yes |
0.000004 |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Lochbaum 2023 |
Single family with a single affected female individual presenting with recurrent edema of the limbs, lips, face, abdomen, lasting approx. five days |
F |
no |
Germany |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
A Portugese population with 38 probands carrying a c.983C>A variant.
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Dias de Castro 2024 |
ClinVar-SCV002240385.3 |
rs118204456 |
Germline |
yes |
0.000004 |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Dias de Castro 2024 |
A population of 38 probands, presumably 38 families, has been shown as carrying a c.953C>A variant |
- |
no |
Portugal |
- |
- |
- |
- |
- |
38 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
The c.983C>A variant meets the ACMG criteria to be characterized pathogenic PP1, PM1, PM5, PS3, PS4_Mod |
Journal: Saddouk 2024 |
- |
rs11820445 |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
- |
- |
HAE3 |
- |
Journal: Saddouk 2024 |
Case report of HAE-FXII diagnosed during pregnancy with details on the management of recurring attacks in a resource-limited setting with no C1-INH concentrate availability. |
F |
no |
Morocco |
- |
- |
- |
- |
- |
2 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
- |
Journal: Lekhlit 2025 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
- |
- |
HAE3 |
- |
Journal: Lekhlit 2025 |
Single individual |
F |
no |
Morocco |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
p.Thr328Lys |
- |
F12_000008 |
- |
Journal: Veronez 2019 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
- |
- |
HAE3 |
- |
Journal: Veronez 2019 |
Single family |
F |
no |
Brazil |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
First report of a Mexican family with 12 carriers - 8 women and 4 men, including an asymptomatic male carrier. |
Journal: Contreras-Verduzco 2023 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
- |
- |
HAE3 |
- |
Journal: Contreras-Verduzco 2023 |
First description of a Mexican HAE-FXII family. |
F |
no |
Mexico |
- |
- |
- |
- |
- |
12 |
Christian Drouet |
+/+ |
9 |
c.983C>A |
r.(?) |
p.(Thr328Lys) |
Unknown |
ACMG |
pathogenic |
g.176831232G>T |
g.177404231G>T |
- |
- |
F12_000008 |
- |
Journal: García Robledo 2025 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
- |
- |
HAE3 |
- |
Journal: García Robledo 2025 |
A single pregnant female individual suffering from HAE during labor induction |
F |
no |
Spain |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
+/. |
9 |
c.983C>G |
r.(?) |
p.(Thr328Arg) |
Unknown |
ACMG |
pathogenic |
g.176831232G>C |
g.177404231G>C |
c.1032C>G |
- |
F12_000039 |
The first c.983C>G variant that has never been found |
Journal: Dewald 2006 |
VCV000001170.4 |
rs118204456 |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Dewald 2006 |
- |
F |
no |
Germany |
- |
- |
- |
- |
- |
2 |
Christian Drouet |
-?/. |
9 |
c.984G>C |
r.(?) |
p.(Thr328=) |
Unknown |
- |
likely benign |
g.176831231C>G |
g.177404230C>G |
F12(NM_000505.3):c.984G>C (p.T328=) |
- |
F12_000017 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/. |
- |
c.1018+12G>C |
r.(=) |
p.(=) |
Unknown |
- |
likely benign |
g.176831185C>G |
- |
F12(NM_000505.3):c.1018+12G>C |
- |
F12_000065 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/. |
- |
c.1018+13G>C |
r.(=) |
p.(=) |
Unknown |
- |
likely benign |
g.176831184C>G |
g.177404183C>G |
F12(NM_000505.3):c.1018+13G>C |
- |
F12_000015 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-/. |
- |
c.1018+19del |
r.(=) |
p.(=) |
Unknown |
- |
benign |
g.176831186del |
g.177404185del |
F12(NM_000505.4):c.1018+19delG |
- |
F12_000004 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/. |
- |
c.1018+19dup |
r.(=) |
p.(=) |
Unknown |
- |
likely benign |
g.176831186dup |
g.177404185dup |
F12(NM_000505.3):c.1018+19dupG |
- |
F12_000016 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/. |
- |
c.1018+19G>A |
r.(=) |
p.(=) |
Unknown |
- |
likely benign |
g.176831178C>T |
g.177404177C>T |
- |
- |
F12_000007 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/. |
- |
c.1019-5C>T |
r.spl? |
p.? |
Unknown |
- |
likely benign |
g.176831096G>A |
- |
F12(NM_000505.4):c.1019-5C>T |
- |
F12_000032 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+/. |
9i |
c.1019-2A>C |
r.spl? |
p.? |
Unknown |
- |
pathogenic |
g.176831093T>G |
- |
F12(NM_000505.4):c.1019-2A>C |
- |
F12_000045 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/. |
- |
c.1025C>T |
r.(?) |
p.(Pro342Leu) |
Unknown |
- |
likely benign |
g.176831085G>A |
- |
F12(NM_000505.3):c.1025C>T (p.P342L) |
- |
F12_000030 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/. |
- |
c.1027G>C |
r.(?) |
p.(Ala343Pro) |
Unknown |
- |
likely benign |
g.176831083C>G |
g.177404082C>G |
F12(NM_000505.3):c.1027G>C (p.A343P), F12(NM_000505.4):c.1027G>C (p.A343P) |
- |
F12_000014 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
-?/. |
- |
c.1027G>C |
r.(?) |
p.(Ala343Pro) |
Unknown |
- |
likely benign |
g.176831083C>G |
g.177404082C>G |
- |
- |
F12_000014 |
classification based on frequency in 305 unrelated individuals |
PubMed: Le 2019 |
- |
- |
Germline |
- |
frequency 0.023 |
- |
- |
- |
DNA |
SEQ, SEQ-NG |
- |
105 WGS/200 WES |
Healthy/Control |
- |
PubMed: Le 2019 |
analysis 305 unrelated individuals |
- |
- |
Viet Nam |
- |
- |
- |
- |
- |
1 |
Global Variome, with Curator vacancy |
-?/. |
- |
c.1027G>C |
r.(?) |
p.(Ala343Pro) |
Unknown |
- |
likely benign |
g.176831083C>G |
- |
F12(NM_000505.3):c.1027G>C (p.A343P), F12(NM_000505.4):c.1027G>C (p.A343P) |
- |
F12_000014 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+?/. |
10 |
c.1027G>C |
r.(?) |
p.(Ala343Pro) |
Unknown |
- |
likely pathogenic |
g.176831083C>G |
g.177404082C>G |
- |
- |
F12_000014 |
Conflicting interpretations of pathogenicity |
Journal: Gelincik 2014 |
- |
rs183643295 |
De novo |
- |
0.00315 (gnomAD, exome) |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE3 |
- |
Journal: Gelincik 2014 |
Single family |
F |
no |
Turkey |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
+?/. |
10 |
c.1027G>C |
r.(?) |
p.(Ala343Pro) |
Unknown |
- |
likely benign |
g.176831083C>G |
g.177404082C>G |
9775G>C |
- |
F12_000014 |
Conflicting interpretations of pathogenicity.
Factor XII exhibits partially defective prekallikrein cleavage activity. |
Journal: Iijima 2011 |
ClinVar-VCV000225352.7 |
rs183643295 |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
Healthy/Control |
- |
Journal: Iijima 2011 |
Symptomatic carrier with a defective prekallikrein cleavage activity |
M |
- |
Japan |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
-?/. |
- |
c.1027G>C |
r.(?) |
p.(Ala343Pro) |
Unknown |
- |
likely benign |
g.176831083C>G |
- |
F12(NM_000505.3):c.1027G>C (p.A343P), F12(NM_000505.4):c.1027G>C (p.A343P) |
- |
F12_000014 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
+/+ |
10 |
c.1093_1094insC |
r.(?) |
p.(Lys365Thrfs*69) |
Parent #1 |
- |
likely pathogenic (recessive) |
g.176831016_176831017insG |
g.177404013_177404014insG |
c.[1093_1094insC];[1744G>A] |
- |
F12_000062 |
- |
Journal: Kwon 2010 |
- |
- |
Germline |
- |
0.00002643 |
- |
- |
- |
DNA |
SEQ |
blood |
- |
F12D |
- |
Journal: Wong 2010 |
- |
F |
- |
Korea |
- |
- |
- |
- |
- |
1 |
Christian Drouet |