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
+/+
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
Insight class: 5
InSiGHT
-
-
SUMMARY record
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+/.
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
-
-
-
Germline
-
-
-
-
-
DNA
?
-
-
-
-
-
-
-
-
United Kingdom (Great Britain)
-
-
-
-
-
1
Ian Frayling
+/.
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
{Clinvar:Ambry;SCV000275379.1}
-
-
Germline
-
-
-
-
-
DNA
?
-
-
cancer, endometrial
-
-
Mother of proband had endometrial at 62y and colon at 67y
F
-
United States
Asian
-
-
-
-
1
InSiGHT - John-Paul Plazzer
+/.
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
{Clinvar:Ambry;SCV000275379.1}
-
-
Germline
-
-
-
-
-
DNA
?
-
-
?, CRC
-
-
mother CRC 70, brother brain tumor at 10
F
-
United States
Asian/Native American
-
-
-
-
1
InSiGHT - John-Paul Plazzer
+/.
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
{Clinvar:Ambry;SCV000275379.1}
-
-
Germline
-
-
-
-
-
DNA
?
-
-
?, CRC
-
-
60yo Asian/Caucasian F dx with 6-9 adenomatous polyps and CRc AT 40; sister thyroid ca at 30 and breast ca at 53 and then uterine(?)/ovarian(?) at 59, brother CRC 41, mother ovarian at 40, father CRC and prostate in his 70s
F
-
United States
Asian/white
-
-
-
-
1
InSiGHT - John-Paul Plazzer
+/.
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
{Clinvar:Ambry;SCV000275379.1}
-
-
Germline
-
-
-
-
-
DNA
?
-
-
CRC
-
-
76yo Asian F dx with CRC; daughter stomach ca 53, son glioblastoma 12
F
-
United States
Asian
-
-
-
-
1
InSiGHT - John-Paul Plazzer
+/.
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
{Clinvar:Ambry;SCV000275379.1}
-
-
Germline
-
-
-
-
-
DNA
?
-
-
cancer, endometrial
-
-
58yo Asian F dx with endometrial ca at 57, MSH2 and MSH6 absent on IHC
F
-
United States
Asian
-
-
-
-
1
InSiGHT - John-Paul Plazzer
+/.
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
{Clinvar:Ambry;SCV000275379.1}
-
-
Germline
-
-
-
-
-
DNA
?
-
-
cancer, endometrial
-
-
57yo Asian F dx with endometrial ca at 46; mother transitional cell of the ureter at 76 and stomach/pancreatic at 80, brother CRC at 32. Family meets Amsterdam II criteria.
F
-
United States
Asian
-
-
-
-
1
InSiGHT - John-Paul Plazzer
+/.
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
{Clinvar:Ambry;SCV000275379.1}
-
-
Germline
-
-
-
-
-
DNA
?
-
CancerNext-Expanded Panel
CRC, cancer, endometrial
-
-
63yo Asian F w/ endometrial ca @48 and colon ca @63; mom w/ panc ca @63, pat aunt w/ breast ca, pat aunt w/ liver ca, pat aunt w/ colon ca @50s, pat uncle w/ colon ca @50s
F
-
United States
Asian
-
-
-
-
1
InSiGHT - John-Paul Plazzer
+/.
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
{Clinvar:Ambry;SCV000275379.1}
-
-
Germline
-
-
-
-
-
DNA
?
-
CancerNext Panel
Healthy/Control
-
-
sister-ut@46; sister-br@46; sister-br@54; sister-br@42; brother-gallbladder@44
F
-
United States
Filipino
-
-
-
-
1
InSiGHT - John-Paul Plazzer
+/.
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
{Clinvar:Ambry;SCV000275379.1}
-
-
Germline
-
-
-
-
-
DNA
?
-
-
CRC, cancer, endometrial
-
-
48yo Asian F w/ endometrial vca @37 and colon ca @46; mother w/ cervicalca @48, mat aunt w/ liverca @37
F
-
United States
Asian
-
-
-
-
1
InSiGHT - John-Paul Plazzer
+/.
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
{Clinvar:Ambry;SCV000275379.1}
-
-
Germline
-
-
-
-
-
DNA
?
-
ColoNext Panel
CRC
-
-
71yo Asian F w/ colon ca; paternal hx unknown, dad died in 20s
F
-
United States
Asian
-
-
-
-
1
InSiGHT - John-Paul Plazzer
+/.
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
Submitted by ICCon South Australia
-
-
-
Germline
-
-
-
-
-
DNA
SEQ
-
-
?
-
-
Submitted by ICCON South Australia
-
-
Australia
-
-
-
-
-
1
ICCon
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
PubMed: Mangold 2005
-
-
Germline
-
-
-
-
-
DNA
PCR, SEQ
-
-
CRC
-
-
-
?
-
Germany
-
-
-
-
-
1
Peter Propping, Prof. Dr. med.
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
PubMed: Ollila 2006
-
-
Germline
-
-
-
-
-
DNA
?
-
-
?
-
-
-
?
-
-
-
-
-
-
-
1
Michael Woods
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
-
-
-
Germline
-
-
-
-
-
DNA
SEQ
-
-
?
-
-
CAPP2 study
?
-
Germany
-
-
-
-
-
1
Juul Wijnen
+/.
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
{Clinvar:Ambry;SCV000275379.1}
-
-
Germline
-
-
-
-
-
DNA
SEQ
-
MSH2, PALB2, MSH6 seq and del/dup, EPAM del/dup
CRC
-
-
mother endometrial ca dx in 60s; maternal GM CRC and endometrial ca; father bladder ca dx 65; brother dx with bladder ca in 30s?; sister dx with bladder ca in 20s?; multiple maternal aunts and uncles dx with CRC, endometrial, bladder cancers (ages at dx unknown). Close to meeting Amsterdam criteria, but no one dx with Lynch associated cancer under the age of 50.
F
-
United States
white, Asian
-
-
-
-
1
InSiGHT - John-Paul Plazzer
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
-
-
-
Germline
-
-
-
-
-
DNA
PCR, SEQ
-
-
CRC
-
-
-
?
-
Germany
-
-
-
-
-
1
Peter Propping, Prof. Dr. med.
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
-
-
-
Germline
-
-
-
-
-
DNA
PCR, SEQ
-
-
CRC
-
-
-
?
-
Germany
-
-
-
-
-
1
Peter Propping, Prof. Dr. med.
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
-
-
-
Germline
-
-
-
-
-
DNA
PCR, SEQ
-
-
CRC
-
-
-
?
-
Germany
-
-
-
-
-
1
Peter Propping, Prof. Dr. med.
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Parent #1
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
PubMed: Betz 2010
-
-
Germline
-
-
-
-
-
DNA
SEQ
-
-
HNPCC (Lynch)
-
-
-
?
-
Germany
-
-
-
-
-
1
Beate Dr. Betz
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Parent #1
-
pathogenic
g.47643490G>A
g.47416351G>A
G -> A at 998
-
MSH2_000539
-
Bennett (unpublished)
-
-
Germline
-
-
-
-
-
DNA
SEQ
-
-
?
-
-
-
?
-
Australia
-
-
-
-
-
1
INSiGHT group
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
-
-
-
Germline
-
-
-
-
-
DNA
SEQ
-
-
CRC
-
-
-
?
-
Netherlands
-
-
-
-
-
1
Ans M.W. van den Ouweland
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
C333Y
-
MSH2_000539
{GR:113}
PubMed: Chao 2008
-
-
Germline
-
-
-
-
-
DNA
SEQ
-
-
HNPCC (Lynch)
-
-
geogr. origin: Australia;InSiGHT LOVDv2 ID:1000205;
?
-
-
-
-
-
-
-
1
Rolf Sijmons
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
C333Y
-
MSH2_000539
{GR:113}
PubMed: Ollila 2006
-
-
Germline
-
-
-
-
-
DNA
SEQ
-
-
HNPCC (Lynch)
-
-
2 affected patients in this HNPCC family, mean age at onset: 41 years old;InSiGHT LOVDv2 ID:1000206;
?
-
-
-
-
-
-
-
1
Rolf Sijmons
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
C333Y
-
MSH2_000539
{GR:113}
PubMed: Lastella 2006
-
-
Unknown
-
-
-
-
-
DNA
SEQ
-
-
-
-
-
-
?
-
-
-
-
-
-
-
1
Rolf Sijmons
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
C333Y
-
MSH2_000539
{GR:113}
PubMed: Lastella 2006
-
-
Unknown
-
-
-
-
-
DNA
SEQ
-
-
-
-
-
-
?
-
-
-
-
-
-
-
1
Rolf Sijmons
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
C333Y
-
MSH2_000539
{GR:113}
PubMed: Lastella 2006
-
-
Unknown
-
-
-
-
-
DNA
SEQ
-
-
-
-
-
-
?
-
-
-
-
-
-
-
1
Rolf Sijmons
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
C333Y
-
MSH2_000539
{GR:113}
PubMed: Chao 2008
-
-
Unknown
-
-
-
-
-
DNA
SEQ
-
-
-
-
-
-
?
-
-
-
-
-
-
-
1
Rolf Sijmons
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
C333Y
-
MSH2_000539
{GR:113}
PubMed: Chao 2008
-
-
Unknown
-
-
-
-
-
DNA
SEQ
-
-
-
-
-
-
?
-
-
-
-
-
-
-
1
Rolf Sijmons
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
C333Y
-
MSH2_000539
{GR:113}
PubMed: Chao 2008
-
-
Unknown
-
-
-
-
-
DNA
SEQ
-
-
-
-
-
-
?
-
-
-
-
-
-
-
1
Rolf Sijmons
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
C333Y
-
MSH2_000539
{GR:113}
PubMed: Ollila 2006
-
-
Unknown
-
-
-
-
-
DNA
SEQ
-
-
-
-
-
-
?
-
-
-
-
-
-
-
1
Rolf Sijmons
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
C333Y
-
MSH2_000539
{GR:113}
PubMed: Ollila 2006
-
-
Unknown
-
-
-
-
-
DNA
SEQ
-
-
-
-
-
-
?
-
-
-
-
-
-
-
1
Rolf Sijmons
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
PubMed: Ward 2005
-
-
Germline
-
-
-
-
-
DNA
?
-
-
?
-
-
-
?
-
-
-
-
-
-
-
1
Michael Woods
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
Authors describe this variant as affecting protein stability.
PubMed: Ollila 2008
-
-
Germline
-
-
-
-
-
DNA
?
-
-
?
-
-
-
?
-
-
-
-
-
-
-
1
Michael Woods
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
-
-
-
Germline
-
-
-
-
-
DNA
SEQ
-
-
CRC
-
-
-
?
-
Germany
-
-
-
-
-
1
Elke Holinski-Feder
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
-
-
-
Germline
-
-
-
-
-
DNA
SEQ
-
-
CRC
-
-
-
?
-
Germany
-
-
-
-
-
1
Elke Holinski-Feder
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
-
-
-
Germline
-
-
-
-
-
DNA
SEQ
-
-
CRC
-
-
-
?
-
Germany
-
-
-
-
-
1
Elke Holinski-Feder
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
-
-
-
Germline
-
-
-
-
-
DNA
SEQ
-
-
CRC
-
-
-
?
-
Germany
-
-
-
-
-
1
Elke Holinski-Feder
+/.
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
998G>A
-
MSH2_000539
-
Loic Le Marchand and Terrilea Burnett
-
-
Germline
-
-
-
-
-
DNA
SEQ
-
-
?
-
-
Hawaiian proband
?
-
-
-
-
-
-
-
1
INSiGHT group
+/.
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
998G>A
-
MSH2_000539
-
Loic Le Marchand and Terrilea Burnett
-
-
Germline
-
-
-
-
-
DNA
SEQ
-
-
?
-
-
-
?
-
-
-
-
-
-
-
1
INSiGHT group
+/.
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
998G>A
-
MSH2_000539
-
Liying Zhang
-
-
Germline
-
-
-
-
-
DNA
SEQ
-
-
cancer
-
-
BRAF V600E mutation status: n/a; BRAF testing method: ;InSiGHT LOVDv2 ID:1016890;
F
-
-
-
-
-
-
-
1
INSiGHT group
+/.
6
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
-
PubMed: Fazekas-Lavu 2017
-
-
Germline
-
-
-
-
-
DNA
?
-
-
cancer, CRC
-
PubMed: Fazekas-Lavu 2017
The family history included ovarian, endometrial, and colon cancer in several first-degree relatives
F
-
-
-
-
-
-
-
1
InSiGHT - John-Paul Plazzer
+/.
-
c.998G>A
r.(?)
p.Cys333Tyr
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
missense variants or in frame indels
-
MSH2_000539
-
PubMed: Baert-Desurmont 2018
-
-
Germline
-
-
-
-
-
DNA
?
-
-
?
-
PubMed: Baert-Desurmont 2018
-
-
-
France
-
-
-
-
-
1
Stephanie Baert-Desurmont
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
NA
g.47643490G>A
g.47416351G>A
-
-
MSH2_000539
Site directed mutagenesis. Functional analysis demonstrated 1% steady-state levels of MSH2 and a loss of interaction with all MSH2 partners. NOTE: Functional analysis was done on the corresponding yeast allele C345Y.
PubMed: Gammie 2007
-
-
In vitro (cloned)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
NA
g.47643490G>A
g.47416351G>A
C333Y
-
MSH2_000539
{GR:113}
PubMed: Gammie 2007
-
-
In vitro (cloned)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
NA
g.47643490G>A
g.47416351G>A
C333Y
-
MSH2_000539
{GR:113}
PubMed: Gammie 2007
-
-
In vitro (cloned)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
NA
g.47643490G>A
g.47416351G>A
C333Y
-
MSH2_000539
{GR:113}
PubMed: Gammie 2007
-
-
In vitro (cloned)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
NA
g.47643490G>A
g.47416351G>A
C333Y
-
MSH2_000539
{GR:113}
PubMed: Ollila 2006
-
-
In vitro (cloned)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
NA
g.47643490G>A
g.47416351G>A
C333Y
-
MSH2_000539
{GR:113}
PubMed: Ollila 2006
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-
In vitro (cloned)
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-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+/.
6
c.998G>A
r.998g>a
p.Cys333Tyr
Unknown
-
NA
g.47643490G>A
g.47416351G>A
C333Y
-
MSH2_000539
{GR:113}
PubMed: Ollila 2006
-
-
In vitro (cloned)
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-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+/.
-
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
pathogenic
g.47643490G>A
g.47416351G>A
MSH2(NM_000251.2):c.998G>A (p.C333Y)
-
MSH2_000539
VKGL data sharing initiative Nederland
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-
-
CLASSIFICATION record
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-
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-
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-
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-
-
-
-
-
-
-
-
-
-
-
?/.
-
c.998G>A
r.(?)
p.(Cys333Tyr)
Parent #1
-
NA
g.47643490G>A
-
chr2_47643490_G_A
-
MSH2_000539
the study was not designed to clinically classify individual variants but performed burden-type association analyses, grouping certain variant types
PubMed: Dorling 2021 , Journal: Dorling 2021
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Germline
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1/60466 cases
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-
DNA
SEQ-NG
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34-gene panel
cancer, breast
-
PubMed: Dorling 2021 , Journal: Dorling 2021
analysis 60466 cases (BRIDGES)
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-
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-
bcac.ccge.medschl.cam.ac.uk/contact
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1
BRIDGES consortium
?/.
-
c.998G>A
r.(?)
p.(Cys333Tyr)
Parent #1
-
NA
g.47643490G>A
-
chr2_47643490_G_A
-
MSH2_000539
the study was not designed to clinically classify individual variants but performed burden-type association analyses, grouping certain variant types
PubMed: Dorling 2021 , Journal: Dorling 2021
-
-
Germline
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1/53461 controls
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-
-
DNA
SEQ-NG
-
34-gene panel
Healthy/Control
-
PubMed: Dorling 2021 , Journal: Dorling 2021
analysis 53461 controls (BRIDGES)
-
-
-
-
-
-
bcac.ccge.medschl.cam.ac.uk/contact
-
1
BRIDGES consortium
-/.
-
c.998G>A
r.(?)
p.(Cys333Tyr)
Unknown
-
NA
g.47643490G>A
-
-
-
MSH2_000539
RNA DATA pCAS2 minigene splicing assay in HeLa cells 2 independent experiments (Inserm U1245, Rouen, France: No effect on exon 6 splicing
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In vitro (cloned)
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