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_8_ |
c.-2332054_*136672dup |
r.0? |
p.0? |
Unknown |
ACMG |
VUS |
g.55033164_57518726dup |
g.55265691_57751253dup |
- |
- |
SERPING1_000776 |
Long duplicated sequence encompassing the entire SERPING1 gene.
Introduced as VUS in ClinVar by GenomeConnect Lewisburg PA; no assertion provided |
- |
ClinVar-000684481 |
- |
De novo |
- |
- |
- |
- |
- |
DNA |
FISH |
- |
- |
HAE1;HAE2 |
- |
- |
- |
- |
- |
United States |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| ?/-? |
_1_8_ |
c.-218202_*285168dup |
r.0? |
p.0? |
Unknown |
- |
benign |
g.57147016_57667222dup |
g.57379543_57899749dup |
- |
- |
SERPING1_000778 |
Long duplicated sequence encompassing the whole SERPING1 gene.
Introduced as benign variant in Clinvar by Cincinnati Children's Hospital Medical Center Genetics and Genomics Diagnostic Laboratory, Cincinnati OH; no assertion provided |
- |
ClinVar-000613420 |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
- |
- |
- |
- |
United States |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| ?/-? |
_1_8_ |
c.-59207_*287295dup |
r.0? |
p.0? |
Unknown |
- |
benign |
g.57306011_57669349dup |
g.57538538_57901876dup |
- |
- |
SERPING1_000777 |
- |
- |
ClinVar-000613421 |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
- |
Single family |
- |
no |
United States |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +?/-? |
_1 |
c.-7913G>A |
r.(=) |
p.(=) |
Unknown |
- |
likely benign |
g.57357305G>A |
g.57589832G>A |
- |
- |
SERPING1_000331 |
Significant difference in higher C1-INH antigenic levels in AMD cases versus controls. |
Journal: Gibson 2012 |
- |
rs2649663 |
Germline |
- |
0.1757 |
- |
- |
- |
DNA |
SEQ |
- |
- |
maculopathy |
- |
- |
- |
- |
- |
United Kingdom (Great Britain) |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
_1_2 |
c.-1998_98del |
r.? |
p.? |
Unknown |
ACMG |
pathogenic |
g.57363220_57367398del |
g.57595747_57599925del |
Large deletion 4.18 kb |
- |
SERPING1_001031 |
A 4.18-kb deletion encompassing entire exons 1 and 2 and a 5' section of exon 3 |
Journal: Ren 2023 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ-NG-I |
blood |
- |
HAE1;HAE2 |
- |
Journal: Ren 2023 |
Single family |
F |
no |
United States |
- |
- |
- |
- |
- |
3 |
Christian Drouet |
| +/+ |
_1_3 |
c.-953_345del |
r.? |
p.? |
Unknown |
ACMG |
pathogenic |
g.57364265_57367645del |
g.57596792_57600172del |
- |
- |
SERPING1_001095 |
Variant resulting in the deletion of exons 1-2 and part of exon 3 (c.-953_345del)
Submitted to ClinVar as pathogenic by InVitae, San Francisco CA |
- |
ClinVar-SCV005064300.1 |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
- |
- |
- |
- |
(United States) |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
_1_8_ |
c.(-387?)_(*422?)del |
r(0?) |
p(0?) |
Unknown |
ACMG |
pathogenic |
g.(57364832?)_(57382477?)del |
g.(57597359?)_(57615004?)del |
9.3 Mb interstitial deletion of chromosome 11 including at least a small sequence of the short arm and a larger region of the long arm and encompassing exons 1 to 8 |
- |
SERPING1_000731 |
- |
Journal: Ebo 2019 |
- |
- |
De novo |
yes |
- |
- |
- |
- |
DNA |
SNPlex |
- |
Unusual pericentromeric rearrangement of chromosome 11 including the SERPING1 gene |
HAE1;HAE2 |
- |
- |
Single family |
M |
no |
Belgium |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
_1_8_ |
c.(-387?)_(*422?)del |
r(0?) |
p(0?) |
Unknown |
ACMG |
pathogenic |
g.(57364832?)_(57382477?)del |
g.(57597359?)_(57615004?)del |
whole gene deletion from exon 1 to exon 8 |
- |
SERPING1_000731 |
Deletion variant with unidentified boundaries |
Journal: Markocsy 2024 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
MAPH |
blood |
- |
HAE1;HAE2 |
- |
Journal: Markocsy 2024 |
Single family |
- |
no |
Slovakia (Slovak Republic) |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
_1_2i |
c.-387_52-123del |
r.? |
p.? |
Unknown |
ACMG |
pathogenic |
g.57364831_57367229del |
g.57597358_57599756del |
- |
- |
SERPING1_000732 |
a 2,399-nt deletion variant encompassing exons 1 to 2 |
Journal: Roche 2005 Journal: Loules 2018 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ-NG-IT |
blood |
- |
HAE1;HAE2 |
- |
- |
Single family |
- |
no |
Spain |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
_1_8_ |
c.-387_*422del |
r.(0?) |
p.(0?) |
Unknown |
ACMG |
pathogenic |
g.57364832_57382477del |
g.57597359_57615004del |
- |
- |
SERPING1_000731 |
a 17,646-nt deletion variant encompassing exons 1 to 8 |
Journal: Roche 2005 Journal: Loules 2018 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ-NG-IT |
blood |
- |
HAE1;HAE2 |
- |
- |
Four independent pedigrees have been recorded to carry a long 17,645-kb deletion encompassing exons 1 to 8
Families 1 & 2, Spain
Families 3 & 4, Greece |
- |
- |
Spain |
- |
- |
- |
- |
- |
4 |
Christian Drouet |
| +?/+? |
1 |
c.-163C>T |
r.(=) |
p.(=) |
Both (homozygous) |
ACMG |
pathogenic (recessive) |
g.57365055C>T |
g.57597582C>T |
c.[-103C>T];[-103C>T] |
- |
SERPING1_000185 |
c.-163C>T variant is the sole idiomorphic nucleotide change in the kindred, found homozygous in the proband, at variance with the dominant mode of transmission observed for structural mutations.
Pathogenic when homozygous, with severe HAE. and low C1-INH levels; homozygosity because of consanguinity.
Variant altering the first nucleotide of a putative CAAT box, the first promoter variant reported in the SERPING1 gene.
In contrast, heterozygous individuals display C1-INH levels within the normal range, although often at its lower level, and were free of angioedema attacks. |
PubMed: Verpy 1996 |
ClinVar-000003956 |
rs1387768389 |
Germline |
no |
0.000007 (gnomAD) |
- |
- |
- |
DNA |
QMPSF |
blood |
Quantitative Multiplex PCR of Short Fluorescent fragments |
HAE1;HAE2 |
- |
PubMed: Verpy 1996 |
A family with 2 homozygous individuals and 4 asymptomatic heterozygous carriers. |
- |
yes |
- |
- |
- |
- |
- |
- |
2 |
Christian Drouet |
| +?/+? |
1 |
c.-161A>G |
r.(=) |
p.(=) |
Both (homozygous) |
ACMG |
pathogenic (recessive) |
g.57365057A>G |
g.57597584A>G |
c.-101A>G |
- |
SERPING1_000186 |
Putatively disrupts CAAT box.
One homozygous proband presenting with a HAE-I phenotype; two homozygous affected siblings.
Heterozygous carriers have been recorded as unaffected indicating a recessive c.-(161)A>G variant.
Introduced in ClinVar by Research Centre for Medical Genetics, Moscow Russia that indicated variant -161A>G meets ACMG /ClinGen criteria to be classified as pathogenic: PS3, PP1_Str, PS4_Mod, PM2_Sup.
Erroneously published as c.-101A>G |
Journal: Büyüköztürk 2009 Journal: Kesim 2011 |
ClinVar-SCV005061388.1 |
rs766344850 |
Germline |
no |
0.0000319 (gnomAD) |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
Journal: Büyüköztürk 2009 Journal: Kesim 2011 |
Two families have been found as carrying a c.-161A>G variant
Family 1, Turkey; only homozygous female proband and her sisters have been recorded as symptomatic. Heterozygous carriers have been recorded as asymptomatic.
Family 2, Azerbaidjan; with 2 homozygous siblings. |
F |
- |
Turkey |
- |
- |
- |
- |
- |
5 |
Christian Drouet |
| +/+ |
1;1 |
c.[-161A>G];[-161A>G] |
r.(=) |
p.(=) |
Both (homozygous) |
ACMG |
pathogenic (recessive) |
g.57365057A>G |
g.57597584A>G |
c.-101A>G; g.[57365057A>G];[57365057A>G] |
- |
SERPING1_000900 |
Regulatory c.–161A>G variant is coordinated to -687 relative to initiation codon; it changed the sequence of -CAAT- box in 5'UTR, with subsequent reduced level of C1-INH mRNA in the homozygous proband comparatively to that is shown in heterozygous individuals. |
Journal: Büyüköztürk 2009 Journal: Kesim 2011 |
- |
- |
Germline |
no |
- |
- |
- |
- |
DNA |
SEQ |
- |
- |
HAE1;HAE2 |
- |
- |
- |
- |
- |
Turkey |
- |
- |
- |
- |
- |
3 |
Christian Drouet |
| ?/? |
1 |
c.-105C>A |
r.(=) |
p.(=) |
Unknown |
ACMG |
VUS |
g.57365113C>A |
g.57597640C>A |
- |
- |
SERPING1_000815 |
- |
- |
ClinVar-000305010 |
rs886048397 |
CLASSIFICATION record |
- |
0.00006 (TOPMed) |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
| ?/. |
1 |
c.-100C>G |
r.(=) |
p.(=) |
Parent #1 |
ACMG |
VUS |
g.57365118C>G |
g.57597645C>G |
c.-40C>T |
- |
SERPING1_000182 |
Pathogenic variant when in a cis configuration with variant c.506T>C.
Variant c.-100C>G affecting a pyrimidine-rich region (c.-108 to c.-77) of potential H-DNA structure. |
PubMed: Verpy 1996 Journal: Ponard 2019 |
ClinVar-000877957 |
rs578018379 |
Germline |
yes |
0.0002 (1000Genomes) |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
Journal: Ren 2023 |
Recurrent variant.
Carrying families in France, United States, Italy, Spain, China. |
- |
no |
- |
- |
- |
- |
- |
- |
14 |
Christian Drouet |
| -?/-? |
1 |
c.-100C>G |
r.(=) |
p.(=) |
Unknown |
- |
likely benign |
g.57365118C>G |
g.57597645C>G |
[-100C>G;816_818del] |
- |
SERPING1_000901 |
- |
PubMed: Verpy 1996 |
- |
- |
Germline |
? |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
- |
- |
- |
- |
France |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| ?/-? |
1 |
c.-99C>G |
r.(=) |
p.(=) |
Unknown |
- |
VUS (!) |
g.57365119C>G |
g.57597646C>G |
- |
- |
SERPING1_001029 |
Introduced as VUS in ClinVar by Illumina, San Diego CA, and benign by Prevention Genetics, Marshfield WI; methods: clinical testing, no C1-INH function analysis |
- |
ClinVar-SCV000372543.3 |
rs866115469 |
Germline |
- |
0.00010 |
- |
- |
- |
DNA |
? |
- |
- |
Healthy/Control |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| ?/. |
1 |
c.-99dup |
r.(=) |
p.(=) |
Unknown |
ACMG |
likely benign |
g.57365119dup |
g.57597646dup |
- |
- |
SERPING1_000857 |
- |
- |
ClinVar-SCV000372541.2 |
rs28362939 |
Germline |
- |
0.001203 (TOPMed); 0.0080 (40/5008; 1000 Genome) |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| -?/-? |
1 |
c.-66_-65del |
r.(?) |
p.(=) |
Unknown |
- |
likely benign |
g.57365152_57365153del |
g.57597679_57597680del |
- |
- |
SERPING1_000330 |
- |
Journal: Roche 2005 |
- |
rs917061427 |
Germline |
- |
0.000056 (TOPMed) |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
Journal: Roche 2005 |
A single observation probably associated with healthy individuals |
- |
- |
Spain |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| -?/-? |
1 |
c.-58T>C |
r.(=) |
p.(=) |
Unknown |
- |
benign |
g.57365160T>C |
g.57597687T>C |
c.-584T>C |
- |
SERPING1_000333 |
Variant found in one control |
Journal: Roche 2005 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
- |
- |
- |
- |
Spain |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| -?/-? |
1 |
c.-56T>G |
r.(=) |
p.(=) |
Unknown |
ACMG |
VUS |
g.57365162T>G |
g.57597689T>G |
- |
- |
SERPING1_000335 |
Introduced in ClinVar as VUS by Illumina Laboratory Services, San Diego CA |
- |
ClinVar-SCV000372544.3 |
rs886048398 |
Germline |
- |
- |
- |
- |
- |
DNA |
SEQ |
- |
- |
HAE1;HAE2 |
- |
- |
- |
- |
- |
United Kingdom (Great Britain) |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
1_8_ |
c.-35_*263del |
r.? |
p.? |
Unknown |
ACMG |
pathogenic |
g.57365183_57382317del |
g.57597710_57614844del |
- |
- |
SERPING1_000838 |
- |
Journal: Loli-Ausejo 2021 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
SEQ |
- |
- |
HAE1;HAE2 |
- |
Journal: Loli-Ausejo 2021 |
- |
- |
- |
Spain |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| -?/. |
1 |
c.-24G>C |
r.(=) |
p.(=) |
Unknown |
ACMG |
likely benign |
g.57365194G>C |
g.57597721G>C |
- |
- |
SERPING1_000336 |
- |
- |
ClinVar-RCV000312741.2 |
rs112290300 |
Germline |
- |
0.00026 (gnomAD); 0.000725 (TOPMed) |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
_1_2i |
c.(-191_-23)_(51+1_52-1)del |
r.0? |
p.0? |
Unknown |
ACMG |
pathogenic |
g.(57365027_57365195)_(57365795_57367351)del |
g.(57597554_57597722)_(57598322_57599878)del |
exons 1_2 deletion of unknown length |
- |
SERPING1_000751 |
c.(-191_-23)_(51+1_52-1)del variant carried by a de novo proband
Considered as pathogenic in agreement with ACMG criteria PVS1, PS2_Str, PS3, PS4, PP4 |
Journal: Lopez-Lera 2011 Journal: Ponard 2019 Journal: Wang 2022 |
- |
- |
De novo |
yes |
- |
- |
- |
- |
DNA |
MAQ |
- |
- |
HAE1;HAE2 |
- |
- |
Four pedigrees have been recorded to carry a long deletion encompassing exons 1 and 2
Family 1, Spain
Family 2, France
Family 3, France
Family 4, China |
- |
- |
Spain |
- |
- |
- |
- |
- |
4 |
Christian Drouet |
| +/+ |
_1_2i |
c.(-191_-23)_(51+1_52-1)del |
r.0? |
p.0? |
Unknown |
ACMG |
pathogenic |
g.(57365027_57365195)_(57365795_57367351)del |
g.(57597554_57597722)_(57598322_57599878)del |
4.18-kb deletion encompassing exons 1 and 2 |
- |
SERPING1_000751 |
Boundaries uncovered by WGS |
Journal: Ren 2023 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ-NG |
blood |
- |
HAE1;HAE2 |
- |
Journal: Ren 2023 |
Single family |
- |
no |
United States |
- |
- |
- |
- |
- |
3 |
Christian Drouet |
| +/+ |
_1_3i |
c.(-191_-23)_(550+1_551-1)del |
r.0? |
p.0? |
Unknown |
ACMG |
pathogenic |
g.(57365027_57365195)_(57367851_57369507)del |
g.(57597554_57597722)_(57600378_57602034)del |
4-kb deletion encompassing exons 1 to 3 |
- |
SERPING1_000769 |
2.8 kb deletion of the genomic region encompassing exons 1-3 of the SERPING1 gene
Introduced in ClinVar as pathogenic variant by InVitae |
PubMed: Stoppa-Lyonnet 1991 Journal: Ponard 2019 |
ClinVar-SCV002243450.2 |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
RFLP |
- |
- |
HAE1;HAE2 |
- |
- |
Two independent families have been found as carrying a long deletion variant encompassing exons 1 to 3
Family 1, France
Family 2, United States of America |
- |
no |
France |
- |
- |
- |
- |
- |
2 |
Christian Drouet |
| +/+ |
_1_4i |
c.(-191_-23)_(685+1_686-1)del |
r.0? |
p.0? |
Unknown |
ACMG |
pathogenic |
g.(57365027_57365195)_(57369643_57373482)del |
g.(57597554_57597722)_(57602170_57606009)del |
exons 1_4 deletion with a 9-kb deletion |
- |
SERPING1_000752 |
- |
PubMed: Stoppa-Lyonnet 1991 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
RFLP |
blood |
- |
HAE1;HAE2 |
- |
- |
Single family |
- |
no |
Spain |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
_1_4i |
c.(-191_-23)_(685+1_686-1)del |
r.0? |
p.0? |
Unknown |
ACMG |
pathogenic |
g.(57365027_57365195)_(57369643_57373482)del |
g.(57597554_57597722)_(57602170_57606009)del |
exons 1_4 deletion with unknown length |
- |
SERPING1_000752 |
- |
PubMed: Duponchel 2001 Journal: Johnsrud 2015 Journal: Ponard 2019 Journal: Loli-Ausejo 2021 Journal: Hashimura 2021 Journal: Wang 2022 |
ClinVar-SCV002243450.2 |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
MAQ |
blood |
- |
HAE1;HAE2 |
- |
- |
Six independent pedigrees have been recorded to carry a long deletion encompassing exons 1 to 4 (unknown length)
Family 1, France
Family 2, Norway
Family 3, France
Family 4, Spain
Family 5, Japan
Family 6, China |
- |
no |
France |
Norway, Spain, Japan |
- |
- |
- |
- |
6 |
Christian Drouet |
| +/+ |
_1_6i |
c.(-191_-23)_(1029+1_1030-1)del |
r.0? |
p.0? |
Unknown |
ACMG |
pathogenic |
g.(57365027_57365195)_(57374021_57379189)del |
g.(57597554_57597722)_(57606548_57611716)del |
exons 1_6 deletion with a 9.3-kb deletion |
- |
SERPING1_000753 |
- |
Journal: Aradhya 2012 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
MAQ |
blood |
- |
HAE1;HAE2 |
- |
- |
Single family |
- |
no |
(United States) |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
_1_6i |
c.(-191_-23)_(1029+1_1030-1)del |
r.0? |
p.0? |
Unknown |
ACMG |
pathogenic |
g.(57365027_57365195)_(57374021_57379189)del |
g.(57597554_57597722)_(57606548_57611716)del |
large deletion (17-kb long) of exons 1 to 6 |
- |
SERPING1_000753 |
- |
PubMed: Stoppa-Lyonnet 1991 Journal: Ponard 2019 Journal: Förster 2021 |
ClinVar-SCV003790197.1 |
- |
Germline |
yes |
- |
- |
- |
- |
RNA |
MAQ |
blood |
- |
HAE1;HAE2 |
- |
- |
Three independent pedigrees have been recorded to carry a long (17-kb) deletion encompassing the first 6 exons with an additional flanking 5' intron 6 sequence
Families 1 and 2, France
Family 3, Germany (n=1) |
- |
- |
France |
Germany |
- |
- |
- |
- |
3 |
Christian Drouet |
| +/+ |
_1_6i |
c.(-191_-23)_(1029+1_1030-1)del |
r.0? |
p.0? |
Unknown |
ACMG |
pathogenic |
g.(57365027_57365195)_(57374021_57379189)del |
rrg.(57597554_57597722)_(57606548_57611716)del |
EX1_6del |
- |
SERPING1_000753 |
A large deletion of unknown length encompassing exons 1 to 6 |
Journal: Grombikirova 2023 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
MLPA |
blood |
- |
HAE1;HAE2 |
- |
Journal: Grombikirova 2023 |
A Czech pedigree with 3 affected individuals |
- |
no |
Czech Republic |
- |
- |
- |
- |
- |
3 |
Christian Drouet |
| +/+ |
_1_7i |
c.(-191_-23)_(1249+1_1250-1)del |
r.0? |
p.0? |
Unknown |
ACMG |
pathogenic |
g.(57365027_57365195)_(57379410_57381800)del |
g.(57597554_57597722)_(57611937_57614327)del |
large deletion encompassing exons 1 to 7 |
- |
SERPING1_000754 |
- |
Journal: Pedrosa 2016 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
MAQ |
blood |
- |
HAE1;HAE2 |
- |
Journal: Pedrosa 2016 |
Single family |
- |
no |
Spain |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
_1_8_ |
c.(-191_-23)_(*272_?)del |
r.0? |
p.0? |
Unknown |
ACMG |
pathogenic |
g.(57365027_57365195)_(57382326_?)del |
g.(57597554_57597722)_(57614853_?)del |
exons 1_8 deletion of unknown length |
- |
SERPING1_000755 |
Recurrent gross deletion
Introduced in ClinVar as a pathogenic variant by InVitae, San Francisco CA |
PubMed: Duponchel 2001 Journal: Roche 2005 Journal: Iwamoto 2012 Journal: Johnsrud 2015 Journal: Ponard 2019 Journal: Loli-Ausejo 2021 Journal: Hashimura 2021 Journal: Szabó 2022 Journal: Grombikirova 2023 |
ClinVar-SCV001591839.3 |
- |
De novo |
yes |
- |
- |
- |
- |
DNA |
MLPA |
blood |
- |
HAE1;HAE2 |
- |
- |
Eleven independent pedigrees have been reported as carrying a long deletion encompassing the exons 1 to 8, unknown length
Family 1, Spain with a probable de novo proband
Family 2, Italy with a non certified de novo proband
Family 3, Japan with a de novo proband
Family 4, France (n=3)
Family 5, Norway
Family 6, Spain
Families 7 & 8, Japan
Family 9, Hungary (n=6)
Families 10 & 11, Czech republic (n=2) |
- |
no |
Spain |
Italy, Japan, France, Norway, Spain, Hungary |
- |
- |
- |
- |
19 |
Christian Drouet |
| +/. |
1i |
c.-23+5del |
r.spl? |
p.? |
Unknown |
- |
VUS |
g.57365200del |
g.57597727del |
-23+5delG |
- |
SERPING1_000012 |
- |
Journal: Ponard 2019 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
- |
Two independent pedigrees have been recorded to carry a c.-23-5G>A variant
Family 1, France (n=2)
Family 2 (n=1) |
- |
- |
France |
- |
- |
- |
- |
- |
3 |
Christian Drouet |
| +/? |
1i |
c.-23+5G>A |
r.(spl)? |
p.0? |
Unknown |
- |
VUS |
g.57365200G>A |
g.57597727G>A |
- |
- |
SERPING1_000016 |
- |
Journal: Ponard 2019 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
- |
Single family |
- |
no |
France |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +?/. |
1i |
c.-23+45T>C |
r.(=) |
p.(=) |
Unknown |
- |
VUS (!) |
g.57365240T>C |
g.57597767T>C |
c.-504T>C |
- |
SERPING1_000334 |
Uncharacterized sequence variant at intron 1.
Found in one patient and one affected relative. Co-segregates with disease. |
Journal: Roche 2005 |
- |
rs183957596 |
Germline |
yes |
0.0052 (TOPMED); 0.00527 (GnomAD); 0.0012 (6/5008, 1000G) |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
- |
One patient and one relative |
- |
- |
Spain |
- |
- |
- |
- |
- |
2 |
Christian Drouet |
| +/+ |
1i |
c.-23+184_-22-152del |
r.(=) |
p.(=) |
Unknown |
ACMG |
likely pathogenic |
g.57365379_57365570del |
g.57597906_57598097del |
- |
- |
SERPING1_000415 |
A 191-nt deletion within intron 1 |
Journal: Ponard 2019 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
- |
- |
- |
no |
France |
- |
- |
- |
- |
- |
2 |
Christian Drouet |
| +/+ |
1i |
c.-22-155G>T |
r.(=) |
p.(=) |
Unknown |
ACMG |
pathogenic |
g.57365567G>T |
g.57598094G>T |
- |
- |
SERPING1_000786 |
The c.-22-155G>T variant introduces in the genome a new donor site stronger than the wild type leading to a larger exon 1 in the RNA level.
The c.-22-155G>T variant disrupts an ISS recognized by a number of transcriptional factors and subsequently stops the suppression of the intronic cryptic donor site.
Transcriptional analysis indicated that the mutant mRNA is susceptible to degradation.
The c.-22-155G > T variant co-segregated with C1-INH-HAE in all of the 4 analyzed patients, while it was absent from 3 healthy family members.
The c.-22-155G > T variant meets ACMG criteria to be considered pathogenic: PS3, PS4, PM2, PP1_Str, PP3, PP4 |
Journal: Vatsiou 2020 |
ClinVar-000870444 |
rs1945307391 |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ-NG-IT |
blood |
- |
HAE1;HAE2 |
- |
- |
Single family |
- |
no |
Greece |
- |
- |
- |
- |
- |
4 |
Christian Drouet |
| +/+? |
1i |
c.-22-25_-22-9del |
r.spl? |
p.0? |
Unknown |
- |
VUS |
g.57365697_57365713del |
g.57598224_57598240del |
-22-25_-9del |
- |
SERPING1_000017 |
- |
Journal: Ponard 2019 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
- |
Single family |
- |
no |
- |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
1i |
c.-22-19_-22-4del |
r.spl? |
p.? |
Unknown |
ACMG |
likely pathogenic |
g.57365703_57365718del |
g.57598230_57598245del |
- |
- |
SERPING1_000018 |
Mutation near splice site in SERPING1 transcript 1. |
Journal: Ponard 2019 Journal: Obtulowicz 2020 Journal: Grombirikova 2023 |
- |
- |
De novo |
yes |
- |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
Journal: Grombirikova 2023 |
Three independent kindreds have been reported as carrying a c.-22-19_-22- 4del variant
Family 1, France (n=2)
Family 2, Poland with a de novo male proband
Family 3, Czech Republic (n=2) |
- |
no |
France |
Poland |
- |
- |
- |
- |
5 |
Christian Drouet |
| +/+ |
1i |
c.-22-10_-22-7del |
r.(=) |
p.(=) |
Unknown |
- |
likely pathogenic |
g.57365712_57365715del |
g.57598239_57598242del |
c.-22-10_-7delGGCT |
- |
SERPING1_000019 |
Transcript expression failed.
Family presenting with a compound heterozygous situation c.[(-21)T>C](;)[-22-10_-22-7del] in a trans configuration (n=2) and in both cis and trans configurations (n=1), with clinical phenotype affected;
-patient 1, female, c.[(-21)T>C];[-22-10_-22-7del];[(-21)T>C], severe;
-patient 2, female, c.[(-21)T>C];[-22-10_-22-7del], moderate;
-patient 3, male, c.[(-21)T>C];[-22-10_-22-7del], mild |
Journal: Ponard 2019 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
- |
Proband presenting with a HAE type I phenotype; one family with 4 affected individuals |
- |
no |
France |
- |
- |
- |
- |
- |
4 |
Christian Drouet |
| +/+? |
1i |
c.-22-7_-22-3del |
r.spl? |
p.? |
Unknown |
- |
VUS |
g.57365715_57365719del |
g.57598242_57598246del |
-22-7_-3delTCCGC |
- |
SERPING1_000020 |
c.-22-7_-22-3delTCCGC variant might affect the acceptor splice site of intron 1. Additional investigations on transcripts are expected. |
Journal: Ponard 2019 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
- |
Single family |
- |
no |
Spain |
- |
- |
- |
- |
- |
2 |
Christian Drouet |
| +/+? |
1i |
c.-22-3C>G |
r.spl? |
p.? |
Unknown |
ACMG |
likely pathogenic |
g.57365719C>G |
g.57598246C>G |
- |
- |
SERPING1_001125 |
The c.-22-3C>G variant in SERPING1 meets ACMG/ClinGen criteria to be classified as likely pathogenic: PP4_Str, PS1_Mod, PM2_Sup, PP3.
Introduced in ClinVar as likely pathogenic by Research Centre For Medical Genetics, Moscow Russia |
- |
ClinVar-SCV005077925.1 |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
? |
blood |
- |
HAE1;HAE2 |
- |
- |
Single family with 2 female and male affected individuals |
- |
no |
Russia |
- |
- |
- |
- |
- |
2 |
Christian Drouet |
| +/+ |
1i |
c.-22-2A>C |
r.spl? |
p.0? |
Unknown |
ACMG |
pathogenic |
g.57365720A>C |
g.57598247A>C |
c.-22-2A>C |
- |
SERPING1_000135 |
- |
Journal: Aabom 2017 |
- |
- |
Germline/De novo (untested) |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
Journal: Aabom 2017 |
Single family with 10 affected individuals |
M |
no |
Denmark |
- |
- |
- |
- |
- |
10 |
Christian Drouet |
| +/+ |
1i |
c.-22-2A>G |
r.spl? |
p.0? |
Unknown |
ACMG |
pathogenic |
g.57365720A>G |
g.57598247A>G |
c.-22-2A>G |
- |
SERPING1_000134 |
Recurrent variant
c.-22-2A>G variant is likely to affect the acceptor splice site of intron 1.
Variant with responsibility for decreased C1 Inhibitor function and HAE |
Journal: Bygum 2011 Journal: Veronez 2019 Journal: Ponard 2019 Journal: Hashimura 2021 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
- |
Four independent pedigrees have been recorded to carry a c.-22-2A>G variant
Family 1, Denmark (n=10)
Family 2, Northern Africa (n=5)
Family 3, Japan
Family 4, Brazil |
- |
- |
France |
- |
- |
- |
- |
- |
17 |
Christian Drouet |
| +/+ |
1i |
c.-22-2A>T |
r.spl? |
p.0? |
Unknown |
ACMG |
pathogenic |
g.57365720A>T |
g.57598247A>T |
- |
- |
SERPING1_000021 |
- |
Journal: Ponard 2019 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
- |
Single family |
- |
no |
Spain |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
1i |
c.-22-1G>A |
r.-22_51del |
p.? |
Unknown |
ACMG |
pathogenic |
g.57365721G>A |
g.57598248G>A |
- |
- |
SERPING1_000137 |
Recurrent variant
Variant that affects intron 1 acceptor splice site, with subsequent partial to complete exon 2 skipping.
Introduced in ClinVar as pathogenic by Research Centre for Medical Genetics, Moscow Russia, indicating variant c.-22-1G>A meets ACMG/ClinGen criteria to be classified as pathogenic: PVS1, PP4_Str, PS4_Mod, PM2_Sup. |
PubMed: Verpy 1996 Journal: Gösswein 2008 Journal: Rijavec 2013 Journal: Andrejević 2015 Journal: Loules 2018 |
ClinVar-SCV005077924.1 |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
- |
Six independent pedigrees have been recorded to carry a c.-22-1G>A variant
Family 1, France
Family 2, Germany (n=2)
Family 3, Slovenia
family 4, Serbia
Family 5, Bulgaria
Family 6, Russia (n=5) |
- |
no |
France |
- |
- |
- |
- |
- |
11 |
Christian Drouet |
| +/+ |
1i_2i |
c.(-23+1_-22-1)_(51+1_52-1)del |
r.(?) |
p.(0?) |
Unknown |
ACMG |
pathogenic |
g.(57365196_57365721)_(57365795_57367351)del |
g.(57597723_57598248)_(57598322_57599878)del |
- |
- |
SERPING1_000756 |
exon 2 deletion, probably encompassing introns 1 and 2 |
Journal: Lopez-Lera 2011 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
MAQ |
blood |
- |
HAE1;HAE2 |
- |
- |
Single family |
- |
no |
Spain |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
1i_3i |
c.(-23+1_-22-1)_(550+1_551-1)del |
r.spl? |
p.? |
Unknown |
ACMG |
pathogenic |
g.(57365196_57365721)_(57367851_57369507)del |
g.(57597723_57598248)_(57600378_57602034)del |
deletion of exons 2_3 |
- |
SERPING1_000131 |
- |
Journal: Ponard 2019 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
- |
Single family |
- |
no |
- |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
_1_4i |
c.(-191_-22-1)_(685+1_686-1)del |
r.(0?) |
p.(0?) |
Unknown |
ACMG |
pathogenic |
g.(57365027_57365721)_(57369643_57373482)del |
g.(57597554_57598248)_(57602170_57606009)del |
deletion of exons 1 to 4 |
- |
SERPING1_000749 |
9-kb deletion variant identified by RFLP |
PubMed: Stoppa-Lyonnet 1991 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
RFLP |
blood |
- |
HAE1;HAE2 |
- |
- |
Single pedigree |
- |
no |
Spain |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
_2_4_ |
c.(-23+1_-22-1)_(685+1_686-1)del |
r.(52_685del) |
p.(?) |
Unknown |
ACMG |
pathogenic |
g.(57365196_57365721)_(57369643_57373482)del |
g.(57597723_57598248)_(57602170_57606009)del |
exons 2-4 deletion |
- |
SERPING1_000982 |
- |
Journal: Wang 2022 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
MAPH |
blood |
- |
HAE1;HAE2 |
- |
- |
- |
- |
no |
China |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
1i_5i |
c.(-23+1_-22-1)_(889+1_890-1)del |
r.? |
p.0? |
Unknown |
ACMG |
pathogenic |
g.(57365196_57365721)_(57373687_57373880)del |
g.(57597723_57598248)_(57606214_57606407)del |
deletion exons 2_5 |
- |
SERPING1_000132 |
variant identified by FAMA |
Journal: Ponard 2019 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
MAQ |
blood |
- |
HAE1;HAE2 |
- |
- |
Single family |
- |
no |
France |
- |
- |
- |
- |
- |
4 |
Christian Drouet |
| -?/-? |
2 |
c.-21T>C |
r.(?) |
p.(=) |
Unknown |
ACMG |
likely benign |
g.57365723T>C |
g.57598250T>C |
SERPING1(NM_000062.2):c.-21T>C |
- |
SERPING1_000001 |
VKGL data sharing initiative Nederland |
Journal: Duponchel 2006 Journal: Ponard 2019 |
ClinVar-SCV000372547.3 |
rs28362944 |
CLASSIFICATION record |
no |
0.029081 (GnomAD_exome); 0.030270 (TOPMed) |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
| -/-? |
2 |
c.-21T>C |
r.(?) |
p.(=) |
Unknown |
ACMG |
benign |
g.57365723T>C |
g.57598250T>C |
SERPING1(NM_000062.2):c.-21T>C |
- |
SERPING1_000001 |
VKGL data sharing initiative Nederland |
- |
- |
rs28362944 |
CLASSIFICATION record |
- |
0.02908 |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
| -?/-? |
2 |
c.-21T>C |
r.(?) |
p.(=) |
Parent #1 |
ACMG |
likely benign |
g.57365723T>C |
g.57598250T>C |
c.[-566T>C;2650T>C] |
- |
SERPING1_000659 |
Pathogenic compound heterozygosity in a cis combination c.[-21T>C;506T>C]. |
PubMed: Verpy 1996 |
ClinVar-SCV000372547.3 |
rs28362944 |
Germline |
- |
0.0314 (gnomADv3) |
- |
- |
- |
DNA |
SEQ |
blood |
Detection by FAMA |
HAE1;HAE2 |
Pat25 |
PubMed: Verpy 1996 |
Single family |
- |
no |
(France) |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| -/-? |
2 |
c.-21T>C |
r.(=) |
p.(=) |
Maternal (confirmed) |
- |
benign |
g.57365723T>C |
g.57598250T>C |
- |
- |
SERPING1_000001 |
The c.-21 T>C variant positioned in trans with another causal variant in the SERPING1 gene was associated with the higher frequency of attacks, lower age at disease onset and higher clinical severity score (Grombirikova 2023) |
PubMed: Bafunno 2013, Journal: Bafunno 2013 Journal: Grombirikova 2023 |
ClinVar-SCV000372547 |
rs28362944 |
Germline |
- |
0.029081 |
- |
- |
- |
DNA |
SEQ |
blood and buccal cells |
- |
HAE1;HAE2 |
patient |
PubMed: Bafunno 2013, Journal: Bafunno 2013 |
Single family |
F |
yes |
(Italy) |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +?/+? |
2;2 |
c.[-21T>C];[-21T>C] |
r.(-22_51del) |
p.0? |
Both (homozygous) |
ACMG |
likely pathogenic (recessive) |
g.57365723T>C |
g.57598250T>C |
c.-21T>C |
- |
SERPING1_000658 |
exon 2 skipped (minigene transfected in Hep3B cells); variant likely pathogenic when homozygous
Average frequency (large NGS studies) 0.02415
Freq EA 264/8028
Freq AA 27/4024
(omner Ivo F.A.C. Fokkema) |
Journal: Duponchel 2006 Journal: Rijavec 2013 |
ClinVar-RCV000365154.1 |
rs28362944 |
Germline |
no |
0.02893 (gnomAD) 0.014577 (1000Genomes) |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
Journal: Rijavec 2013 |
Homozygous female proband is presenting with a HAE type II phenotype with low grade severity. Heterozygous parents are asymptomatic. |
- |
- |
Slovenia |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
_2_8_ |
c.(-23+1_-22-1)_(*272?)del |
r.(52_*272)del |
p.? |
Unknown |
ACMG |
pathogenic |
g.(57365196_57365721)_(57382326_?)del |
g.(57597723_57598248)_(57614853_?)del |
exon 2-8 deletion with 16,312 bp loss |
- |
SERPING1_001196 |
- |
Journal: Gao 2025 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
MLPA |
- |
- |
HAE1;HAE2 |
- |
Journal: Gao 2025 |
Single family |
- |
no |
China |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
3i_8_ |
c.(550+1_551-1)_(*422?)del |
r.(?) |
p? |
Unknown |
ACMG |
pathogenic |
g.(57367851_57369507)_(57382477?)del |
g.(57600378_57602034)_(57615004?)del |
deletion of exon 4 to 8 |
- |
SERPING1_000898 |
- |
Journal: Hashimura 2021 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
? |
blood |
- |
HAE1;HAE2 |
- |
- |
- |
- |
no |
Japan |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
_1_6_ |
c.(_-163)_(1029+20_1030-1)del |
r.? |
p.? |
Unknown |
ACMG |
pathogenic |
g.(57365055_57374040)del |
g.(57597582_57606567)del |
exons 1-6 deletion |
- |
SERPING1_001097 |
Gross deletion of the genomic region encompassing exons 1-6 of unknown length, which includes the initiation codon. This deletion extends beyond the assayed region for SERPING1 gene and therefore may encompass additional genes. It is expected to result in an absent or disrupted protein product.
Submitted to ClinVar as pathogenic by InVitae, San Francisco CA. |
- |
ClinVar-SCV003790197.3 |
- |
Germline/De novo (untested) |
- |
- |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
- |
- |
- |
- |
(United States) |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
_1_3_ |
c.(_-163)_(550+20_551-1)del |
r.? |
p.? |
Unknown |
ACMG |
pathogenic |
g.(57365055)_(57367870)del |
g.(57597582)_(57600397)del |
exons 1-3 deletion of unknown length |
- |
SERPING1_001098 |
Gross deletion of the genomic region encompassing exons 1-3, which includes the initiation codon. This deletion extends beyond the assayed region for this gene and therefore may encompass additional genes.
Submitted to ClinVar as pathogenic by InVitae, San Francisco CA. |
- |
ClinVar-SCV002243450.4 |
- |
Germline/De novo (untested) |
- |
- |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
- |
- |
- |
- |
(United States) |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
_1_4_ |
c.(_-163)_(685+20_686-1)del |
r.? |
p.? |
Unknown |
ACMG |
pathogenic |
g.(57365055)_(57369662)del |
g.(57597582)_(57602189)del |
exons 1-4 deletion of unknown length |
- |
SERPING1_001099 |
Gross deletion of the genomic region encompassing exons 1-4, which includes the initiation codon. This deletion extends beyond the assayed region for SERPING1 gene and therefore may encompass additional genes.
Submitted to ClinVar as pathogenic by InVitae, San Francisco CA. |
- |
ClinVar-SCV002231896.4 |
- |
Germline/De novo (untested) |
- |
- |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
- |
- |
- |
- |
(United States) |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
_1_4i |
c.-1272_(686-538)del |
r.(-22_685?)del |
p.? |
Unknown |
ACMG |
pathogenic |
g.57363946_57372945del |
g.57596473_57605472del |
g.57363946_57372945del |
- |
SERPING1_001197 |
- |
Journal: Gao 2025 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
Journal: Gao 2025] |
Single family |
- |
no |
China |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| ?/? |
_1_8_ |
c.-191_*272{2} |
r.(=) |
p.(=) |
Unknown |
- |
VUS |
g.57139699_57703639dup |
g.57372226_57936167dup |
- |
- |
SERPING1_000865 |
- |
- |
ClinVar-000058162 |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
DNA |
? |
- |
- |
autism |
- |
Journal: Kaminsky 2011 |
- |
- |
- |
United States |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
7;7 |
c.[1202T>C] |
r.[(1202u>c)] |
p.[(Ile401Thr)] |
Both (homozygous) |
ACMG |
pathogenic (recessive) |
g.57379362T>C |
g.57611889T>C |
g.[57379362T>C];[57379362T>C] |
- |
SERPING1_000725 |
Two homozygous individuals presenting with a more severe clinical phenotype than the single affected heterozygous individual, presenting with a nearly asymptomatic HAE phenotype.
The Ile to Thr substitution at position 401 might affect the function of the gate |
Journal: Mete Gökmen 2020 |
- |
rs1263371770 |
Germline |
no |
0.000004 |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
- |
Single family |
- |
yes |
Turkey |
- |
- |
- |
- |
- |
7 |
Christian Drouet |
| +/+ |
3 |
c.[536C=/>T] |
r.(?) |
p.(Thr179Ile) |
Paternal (confirmed) |
ACMG |
pathogenic |
g.[57367836C=/>T] |
g.[57600363C=/>T] |
- |
- |
SERPING1_001174 |
Gonadal mosaicism in a family in which only both sisters, but not the parents, show clinical and laboratory findings typical of HAE, with allele segregation demonstrated using Sanger sequencing.
c.536C>T variant not detected in DNA derived from lymphocytes from the father and the mother, whereas present on the DNA prepared from the sperm of the father and on the paternal transmitted chromosome. |
Journal: Ebo 2018 |
- |
- |
Uniparental disomy, paternal allele |
yes |
- |
- |
- |
- |
DNA |
SEQ |
lymphocytes, sperm |
- |
HAE1;HAE2 |
- |
Journal: Ebo 2018 |
Single family with parental disomy |
F |
no |
Belgium |
- |
- |
- |
- |
- |
2 |
Christian Drouet |
| +/+ |
4 |
c.[597C=/>G] |
r.(?) |
p.(Tyr199*) |
Unknown |
ACMG |
pathogenic |
g.[57369554C=/>G] |
g.[57602081C=/>G] |
- |
- |
SERPING1_000516 |
Gonadal mosaicism in a family in which only both sons, but not the parents, show clinical and laboratory findings typical of HAE, with allele segregation demonstrated using DHPLC.
c.597C>G variant not not detected in DNA derived from buccal cells, urinary cells, hair roots and cultured fibroblasts from the mother, whereas occurred on the maternal transmitted chromosome. |
Journal: Guarino 2006 |
ClinVar-VCV000003957.1 |
rs121907951 |
Uniparental disomy, maternal allele |
yes |
0.00000 (0/78700) |
- |
- |
- |
DNA |
DHPLC |
blood, buccal, urinary, hair roots, fibroblasts |
- |
HAE1;HAE2 |
- |
- |
A single family with 2 affected sons in a gonadal mosaicism |
- |
no |
Italy |
- |
- |
- |
- |
- |
2 |
Christian Drouet |
| +/+ |
3 |
c.[69_139del/=] |
r.(?) |
p.(Pro24Asnfs*10) |
Paternal (confirmed) |
ACMG |
pathogenic |
g.57367369_57367439del |
g.57599896_57599966del |
- |
- |
SERPING1_000652 |
Erroneously identified as a c.3_73del;p.(Asn1fs*34) variant by Yu et al 2007.
Identified as c.67_137del in IDbases
Gonadal mosaicism in a family in which both brothers, but not the parents, show clinical and laboratory findings typical of HAE, with allele segregation demonstrated using Sanger sequencing.
c.69_139del variant not detected in DNA derived from lymphocytes from the father and the mother, whereas present on the DNA prepared from the sperm of the father. |
Journal: Yu 2007 |
- |
- |
Uniparental disomy, paternal allele |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
Journal: Yu 2007 |
Proband and 2 brothers presenting with HAE type I. A paternal mosaicism has been demonstrated |
M |
- |
Taiwan |
- |
- |
- |
- |
- |
4 |
Christian Drouet |
| +/+ |
5i |
c.[890-1G=/>C] |
r.spl? |
p.? |
Maternal (confirmed) |
ACMG |
pathogenic |
g.[57373880G=/>C] |
g.[57606407G=/>C] |
c.[890-1G=/>C] |
- |
SERPING1_001173 |
Demonstrated exon 6 skiping and an aberrant in-frame insertion of 9-aa residues N-terminus of exon 6.
Despite normal C1-INH function in the parents, the mother was found a mutation carrier. The inverted profile of the Sanger peaks compared with the patient, strongly suggests the presence of gonosomal mosaicism in the mother. |
Journal: Batlle-Masó 2025 |
- |
- |
Uniparental disomy, maternal allele |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
Journal: Batlle-Masó 2025 |
Single family with a gonosomal mosaicism in the mother |
F |
no |
Spain |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
8 |
с.1442_1443insGCTGCGTGCT |
r.(?) |
p.(Trp482Leufs*19) |
Unknown |
ACMG |
pathogenic |
g.57381993_57381994insGCTGCGTGC |
g.57614520_57614521insGCTGCGTGC |
- |
- |
SERPING1_001187 |
- |
Journal: Baysheva 2024 |
- |
- |
Germline/De novo (untested) |
- |
- |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
Journal: Baysheva 2024 |
Single family |
- |
no |
Russia |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
2 |
c.1A>C |
r.(?) |
p.(Met1Leu) |
Unknown |
ACMG |
pathogenic |
g.57365744A>C |
g.57598271A>C |
- |
- |
SERPING1_000464 |
c.1A>C variant affecting the initiation codon of the transcript of SERPING1 gene.
Introduced in ClinVar as pathogenic variant by Department of Immunology and Histocompatibility, University of Thessaly.
Variant validated by the SERPING1-NGS platform using NGS-Ion Torrent by Loules 2018 |
Journal: Speletas 2015 Journal: Loules 2018 |
ClinVar-SCV000900062.1 |
rs1565168898 |
Germline |
- |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
- |
Single family |
M |
no |
Greece |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
2 |
c.1A>G |
r.(1a>g) |
p.(Met1Val) |
Unknown |
ACMG |
pathogenic |
g.57365744A>G |
g.57598271A>G |
c.1A>G |
- |
SERPING1_000147 |
c.1A>G variant affects the initiation codon of the transcript of SERPING1 gene.
Recurrent variant found in multiple pedigrees, Germany, Turkey, Greece, Spain, France, Hungary, China.
One pedigree is presenting with a de novo mutation. According to ACMG Guidelines, with criteria PVS1, PS1, PS2, PS4, PM2, PP1, PP4, the variant is considered pathogenic. |
Journal: Gösswein 2008PubMed: Papadopoulou 2008Journal: Speletas 2009Journal: López-Lera 2011Journal: Bors 2013Journal: Ponard 2019Journal: Szabó 2022 Journal: Wang 2022 |
ClinVar-VCV000626352.1 |
rs1565168898 |
De novo |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
Journal: Gösswein 2008 Journal: Papadopoulou-Alataki 2008 Journal: Speletas 2009 Journal: López-Lera 2011 |
Variant c.1A>G has been reported as carried by eight independent pedigrees from
Germany, 4 families (n=9)
Greece, 1 family (n=6), with a de novo condition
Spain, 1 family
Hungary, 1 family (n=2)
China, 1 family (n=6)
One pedigree is presenting with a de novo mutation |
- |
no |
Germany |
- |
- |
- |
- |
- |
24 |
Christian Drouet |
| +/+ |
2 |
c.1A>T |
r.(?) |
p.(Met1Leu) |
Unknown |
ACMG |
likely pathogenic |
g.57365744A>T |
g.57598271A>T |
- |
- |
SERPING1_000463 |
c.1A>T variant affects the initiation codon required for SERPING1 gene expression |
Journal: Pappalardo 2008 Journal: Kesim 2011 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
- |
Two independent pedigrees have been recorded to carry a c.1A>T variant
Family 1, Italy
Family 2, Turkey (n=3) |
- |
- |
Italy |
- |
- |
- |
- |
- |
4 |
Christian Drouet |
| +/+ |
2 |
c.2T>A |
r.(?) |
p.(Met1Lys) |
Unknown |
ACMG |
pathogenic |
g.57365745T>A |
g.57598272T>A |
- |
- |
SERPING1_000465 |
c.2T>A variant affects the initiation codon of the transcript of SERPING1 gene. |
Journal: Pappalardo 2008 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
- |
Single family |
- |
no |
Italy |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
2 |
c.2T>C |
r.(?) |
p.(Met1Thr) |
Unknown |
ACMG |
pathogenic |
g.57365745T>C |
g.57598272T>C |
- |
- |
SERPING1_000466 |
c.2T>C variant affects the initiation codon of the transcript of SERPING1 gene. |
Journal: Bafunno 2014 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
- |
Single family |
- |
no |
Italy |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +?/+? |
2 |
c.2T>G |
r.(?) |
p.(Met1Arg) |
Unknown |
ACMG |
pathogenic |
g.57365745T>G |
g.57598272T>G |
- |
- |
SERPING1_000467 |
c.2T>G variant affect the initiation codon required for SERPING1 gene expression.
Introduced in ClinVar as pathogenic by Labcorp Genetics, San Francisco CA |
Journal: Loules 2018 |
ClinVar-RCV003734626.1 ClinVar-SCV004538883.1 |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ-NG-IT |
blood |
- |
HAE1;HAE2 |
- |
- |
Single family |
- |
no |
(Greece) |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
2 |
c.3G>A |
r.(?) |
p.(Met1?) |
Unknown |
ACMG |
pathogenic |
g.57365746G>A |
g.57598273G>A |
589G>A (traditional) |
- |
SERPING1_000468 |
p.(Met1Ile) disrupts the initiation codon of SERPING1 gene expression.
Italian paient samples exhibit a high level of circulating cleaved HK species, with 27.7% to 45.8% of total HK, consistent with an involvement of kallikrein-kinin system. |
Journal: Gösswein 2008 Journal: Pappalardo 2008 Journal: Suffritti 2014 Journal: Hashimura 2021 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
- |
Three independent pedigrees have been recorded as carrying a c.3G>A variant
Family 1, Germany
Family 2, Italy (n=3)
Family 3, Japan |
- |
no |
Germany |
- |
- |
- |
- |
- |
5 |
Christian Drouet |
| +/+ |
2_3 |
c.3_73del |
r.? |
p.? |
Unknown |
ACMG |
pathogenic |
g.57365746_57367373del |
g.57598273_57599900del |
- |
- |
SERPING1_000916 |
- |
PubMed: Lei 2011 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
- |
Single family |
- |
no |
Taiwan |
- |
- |
- |
- |
- |
3 |
Christian Drouet |
| +/. |
2 |
c.5C>T |
r.(?) |
p.(Ala2Val) |
Unknown |
- |
pathogenic |
g.57365748C>T |
g.57598275C>T |
SERPING1(NM_000062.2):c.5C>T (p.A2V), SERPING1(NM_000062.3):c.5C>T (p.A2V) |
- |
SERPING1_000002 |
VKGL data sharing initiative Nederland |
- |
ClinVar-000305016 |
rs185342631 |
CLASSIFICATION record |
- |
0.0009841 (gnomAD v3) |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
| -?/-? |
2;7 |
c.5C>T |
r.(?) |
p.(Ala2Val) |
Maternal (confirmed) |
ACMG |
likely benign |
g.57365748C>T |
g.57598275C>T |
[5C>T];[1045C>T] |
- |
SERPING1_000370 |
Likely benign/benign with the following criteria BS1, BS2, BP2, BP4.
Compound heterozygous proband c.[5C>T];[1045C>T] presenting with a HAE of the intermediate type.
Two variants are in trans, c.5C>T maternal allele/c.1045C>T paternal allele, both parents are asymptomatic, proband's sister is not a carrier |
Journal: Ponard 2019 |
ClinVar-000305016 |
rs185342631 |
Germline |
no |
0.0009841 (c.5C>T; gnomAD v3) |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
- |
- |
- |
- |
France |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| ?/-? |
2 |
c.5C>T |
r.(?) |
p.(Ala2Val) |
Parent #1 |
- |
VUS |
g.57365748C>T |
g.57598275C>T |
- |
- |
SERPING1_000002 |
conflicting interpretations of pathogenicity; 14 heterozygous, no homozygous; Clinindb (India) |
PubMed: Narang 2020 Journal: Narang 2020 |
- |
rs185342631 |
Germline |
- |
14/2795 individuals |
- |
- |
- |
DNA |
arraySNP |
- |
Infinium Global Screening Array v1.0 |
? |
- |
PubMed: Narang 2020, Journal: Narang 2020 |
analysis 2794 individuals (India) |
- |
- |
India |
- |
- |
- |
- |
- |
14 |
Mohammed Faruq |
| -?/-? |
2 |
c.5C>T |
r.(?) |
p.(Ala2Val) |
Unknown |
ACMG |
VUS |
g.57365748C>T |
g.57598275C>T |
- |
- |
SERPING1_000002 |
Conflicting presentations of the c.5C>T variant. Introduced in ClinVar as a VUS by Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago.
Variant c.5C>T is carried by 7 affected families.
Families 1 & 2, Germany, 4 affected heterozygous individuals. HAE type not documented.
Family 3, France, with a single affected individual presenting with a HAE type I mild phenotype.
Family 4, France, a family where the proband is a compound heterozygous c.[5C>T];[1045C>T] and the c.5C>T allele is carried by the pauci-symptomatic mother.
Family 5, Denmark, with a c.5C>T carrier associated with anti-C1Inh antibody.
Family 6, Iran, with 2 male patients affected and presenting with a HAE type I phenotype.
Family 7, Belarus (n=1), a young female patient presenting with a HAE type I phenotype since puberty.
Family 8, Turkey (n=2) with a female patient suffering since 2.5 years old (moderate) and a male individual since 10 years old with laryngeal attacks.
Five homozygous carriers c.[5C>T];[5C>T] have been recorded. |
Journal: Gösswein 2008 Journal: Ponard 2019 Journal: Rasmussen 2019 Journal: Nabilou 2020 Journal: Guryanova 2021 Journal: Soyak Aytekin 2021 |
ClinVar-SCV000898969.1 |
rs185342631 |
Germline |
yes |
0.00089 (gnomAD v3); 0.001003 (TOPMED); 0.000799 (1000Genomes) |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
- |
Eight kindreds have been reported as to carry a c.5C>T variant
Families 1 & 2, Germany, with 4 affected individuals carrying c.5C>T
Family 3, France, a single affected individual presenting with a HAE type I phenotype
Family 4, France, with 2 affected compound heterozygous individuals c.[5C>T(;)1045C>T]
Family 5, Denmark, with an individual carrying a c.5C>T variant associated with anti-C1INH antibody
Family 6, Iran, with 2 male patients affected presenting a HAE type I phenotype
Family 7, Belarus, with a single affected female individual, who manifested HAE at the age of 10, skin and abdominal attacks 5 times a year. HAE type not documented.
Family 8, Turkey (n=2) with a female patient suffering since 2.5 years old (moderate) and a male individual since 10 years old from laryngeal attacks. |
- |
no |
Germany |
France, Denmark, Iran, Belarus, Turkey |
- |
- |
- |
- |
13 |
Christian Drouet |
| ?/-? |
2 |
c.5C>T |
r.(?) |
p.(Ala2Val) |
Unknown |
- |
VUS |
g.57365748C>T |
- |
SERPING1(NM_000062.2):c.5C>T (p.A2V), SERPING1(NM_000062.3):c.5C>T (p.A2V) |
- |
SERPING1_000002 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
| -?/-? |
2;8 |
c.5C>T |
r.(?) |
p.(Ala2Val) |
Parent #1 |
ACMG |
VUS |
g.57365748C>T |
g.57598275C>T |
c.[5C>T(;)1397G>A] |
- |
SERPING1_000002 |
Combination of variants c.[5C>T(;)1397G>A] in a single individual presenting with a HAE type 1 phenotype; the pathogenic variant c.1397G>A fully explains the phenotype.
Segregation analysis of c.5C>T in the family not possible, variant c.5C>T supposed having no impact on clinical phenotype and laboratory observations. |
Journal: Markocsy 2024 |
- |
- |
Germline |
? |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
Journal: Markocsy 2024 |
A single individual has been shown as carrying a combined c.[5C>T(;)1397G>A] |
F |
no |
Slovakia (Slovak Republic) |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| ?/. |
- |
c.5C>T |
r.(?) |
p.(Ala2Val) |
Unknown |
- |
VUS |
g.57365748C>T |
- |
SERPING1(NM_000062.2):c.5C>T (p.A2V), SERPING1(NM_000062.3):c.5C>T (p.A2V) |
- |
SERPING1_000002 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
| +/+ |
2 |
c.5_6del |
r.(?) |
p.(Ala2Valfs*17) |
Unknown |
ACMG |
pathogenic |
g.57365748_57365749del |
g.57598275_57598276del |
5_6delCC |
- |
SERPING1_000876 |
- |
Journal: Hashimura 2021 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
SEQ |
- |
- |
HAE1;HAE2 |
- |
- |
- |
- |
- |
Japan |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
2 |
c.6dup |
r.(?) |
p.(Ser3Leufs*17) |
Unknown |
ACMG |
pathogenic |
g.57365749dup |
g.57598276dup |
- |
- |
SERPING1_001106 |
Patient presenting with recurrent and frequent angioedema attacks.
The function and concentration of C1-INH and antigenic C4 of the parents and younger brother are normal. Immediate and closest relatives within 3 generations did not have a angioedema history; the possibility of a sporadic genetic mutation is considered. |
Journal: Zhang 2025 |
- |
- |
Germline/De novo (untested) |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
Journal: Zhang 2025 |
Single affected individual in a family presenting with apparently healthy relatives. |
F |
no |
China |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
2 |
c.6_13del |
r.(?) |
p.(Ser3Aspfs*14) |
Unknown |
ACMG |
pathogenic |
g.57365749_57365756del |
g.57598276_57598283del |
- |
- |
SERPING1_001110 |
The c.6_13del variant in SERPING1 meets ACMG/ClinGen criteria to be classified as pathogenic: PVS1, PP4_Mod, PM2_Sup. |
- |
ClinVar-SCV005186251.1 |
- |
De novo |
yes |
- |
- |
- |
- |
DNA |
? |
blood |
- |
HAE1;HAE2 |
- |
- |
Single family |
M |
no |
Russia |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
2 |
c.6_13dup |
r.(?) |
p.(Leu5Profs*4) |
Unknown |
ACMG |
pathogenic |
g.57365749_57365756dup |
g.57598276_57598283dup |
- |
- |
SERPING1_000138 |
A c.3_10dup was erroneously introduced in SERPING1base, ID @R4X8, accession S0049 on 30 July 2004; structure.bmc.lu.se/idbase/SERPING1base/ |
PubMed: Verpy 1996 Journal: Ponard 2019 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
QMPSF |
- |
Quantitative Multiplex PCR of Short Fluorescent fragments |
HAE1;HAE2 |
- |
PubMed: Verpy 1996 |
Family 1 with 2 affected individuals |
- |
- |
France |
- |
- |
- |
- |
- |
2 |
Christian Drouet |
| +?/+? |
2 |
c.9del |
r.(?) |
p.(Arg4Glyfs*2) |
Unknown |
- |
likely pathogenic |
g.57365752del |
g.57598279del |
- |
- |
SERPING1_000797 |
No functional evidence for this variant
No familial identification was provided |
- |
ClinVar-000830237 |
rs1945310324 |
CLASSIFICATION record |
- |
- |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
- |
- |
- |
- |
Kuwait |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
2 |
c.15_16dup |
r.(?) |
p.(Thr6Argfs*4) |
Unknown |
ACMG |
pathogenic |
g.57365758_57365759dup |
g.57598285_57598286dup |
c.15_16dupGA |
- |
SERPING1_000141 |
Variant introduced in the Lund SERPING1 database http://structure.bmc.lu.se/idbase/SERPING1base/ |
Journal: Zuraw 2000 Journal: Chan 2024 |
- |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
Journal: Zuraw 2000 Journal: Chan 2024 |
Two independent families have been shown as carrying a c.15_16dup variant
-Family 1, United States of America
-Family 2, Australia |
- |
- |
(United States) |
- |
- |
- |
- |
- |
2 |
Christian Drouet |
| +/+ |
2 |
c.17_24dup |
r.(?) |
p.(Thr9Profs*3) |
Unknown |
ACMG |
pathogenic |
g.57365760_57365767dup |
g.57598287_57598294dup |
17_24dupCCCTGCTG |
- |
SERPING1_000877 |
- |
Journal: Hashimura 2021 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
SEQ |
- |
- |
HAE1;HAE2 |
- |
- |
- |
- |
- |
Japan |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
2 |
c.19dup |
r.(?) |
p.(Leu7Profs*13) |
Unknown |
ACMG |
likely pathogenic |
g.57365762dup |
g.57598289dup |
c.19dupC |
- |
SERPING1_000142 |
- |
Journal: Johnsrud 2015 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
Journal: Johnsrud 2015 |
Single family |
- |
no |
Norway |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
2 |
c.23dup |
r.(?) |
p.(Thr9Aspfs*11) |
Unknown |
ACMG |
pathogenic |
g.57365766dup |
g.57598293dup |
c.23insT |
- |
SERPING1_000140 |
- |
Journal: Bygum 2011 Journal: Veronez 2019 |
- |
- |
Germline/De novo (untested) |
- |
- |
- |
- |
- |
DNA |
SEQ |
bloods |
- |
HAE1;HAE2 |
- |
Journal: Bygum 2011 |
Single family with 2 affected individuals |
- |
no |
Denmark |
- |
- |
- |
- |
- |
2 |
Christian Drouet |
| ?/- |
2 |
c.25A>C |
r.(?) |
p.(Thr9Pro) |
Unknown |
ACMG |
benign |
g.57365768A>C |
g.57598295A>C |
- |
- |
SERPING1_000745 |
- |
- |
ClinVar-SCV001726012.4 |
rs201455616 |
Not applicable |
- |
0.000355 (gnomAD) 0.000637 (ExAC) |
- |
- |
- |
DNA |
? |
- |
- |
Healthy/Control |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
2 |
c.29T>G |
r.(?) |
p.(Leu10Arg) |
Unknown |
ACMG |
likely pathogenic |
g.57365772T>G |
g.57598299T>G |
- |
- |
SERPING1_000022 |
Variant Leu10Arg is not expressed after transient transfection of minigene into 293T cells.
Altering the hydrophobic core by substitution by positively charged amino acids can disrupt signal peptide transportation and impair protein secretion. |
Journal: Ponard 2019 Journal: Ren 2025 |
- |
- |
De novo |
yes |
- |
- |
- |
- |
DNA |
? |
- |
- |
HAE1;HAE2 |
- |
- |
Single family with a de novo proband |
- |
no |
Spain |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
2 |
c.32dup |
r.(?) |
p.(Leu12Alafs*8) |
Unknown |
ACMG |
pathogenic |
g.57365775dup |
g.57598302dup |
- |
- |
SERPING1_000342 |
- |
Journal: Mete Gökmen 2019 |
- |
- |
Germline/De novo (untested) |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
Journal: Mete Gökmen 2019 |
Two affected individuals with severe clinical phenotype |
- |
- |
Turkey |
- |
- |
- |
- |
- |
2 |
Christian Drouet |
| +/+ |
2 |
c.33dup |
r.(?) |
p.(Leu12Alafs*8) |
Unknown |
ACMG |
pathogenic |
g.57365776dup |
g.57598303dup |
- |
- |
SERPING1_000343 |
- |
Journal: Pappalardo 2008 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
- |
- |
- |
- |
(Italy) |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
| +/+ |
2 |
c.35T>G |
r.(?) |
p.(Leu12Arg) |
Unknown |
ACMG |
likely pathogenic |
g.57365778T>G |
g.57598305T>G |
- |
- |
SERPING1_000469 |
Simulation by SignalP excludes the possibility that substitutions Leu to Arg has an important role in the proteolytic cleavage after the uptake of the protein into the endoplasmic reticulum.
The variant p.(Leu12Arg) is not expressed when minigene is transfected into 293T cells. Altering the hydrophobic core by substitution with positively charged amino acids can disrupt signal peptide transportation and impair protein secretion.
The c.35T>G variant in SERPING1 meets ACMG/ClinGen SVI guidance criteria to be classified as likely pathogenic: PP4_Mod, PS3, PS4_Mod, PM2_Sup, PP2, PP3 |
Journal: Bafunno 2014 Journal: Ren 2025 |
ClinVar-SCV005088165.1 |
- |
Germline |
yes |
- |
- |
- |
- |
DNA |
SEQ |
blood |
- |
HAE1;HAE2 |
- |
- |
Two independent families have been shown as carrying a c.35T>G variant
Family 1, Italy
Family 2, Russia |
- |
no |
Italy |
- |
- |
- |
- |
- |
2 |
Christian Drouet |
| +/+ |
2 |
c.36dup |
r.(?) |
p.(Leu13Alafs*7) |
Unknown |
ACMG |
pathogenic |
g.57365779dup |
g.57598306dup |
- |
- |
SERPING1_000344 |
- |
Journal: Bafunno 2014 |
- |
- |
Germline |
- |
- |
- |
- |
- |
DNA |
SEQ |
b |
- |
HAE1;HAE2 |
- |
Journal: Bafunno 2014 |
Single family |
M |
no |
Italy |
- |
- |
- |
- |
- |
1 |
Christian Drouet |
