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.
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.
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.
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)
- association
- unclassified
- 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%)
IDbase Accession Number: IDbase Accession Number
VariO/DNA: variation ontology annotation at DNA level
All options:
- DNA substitution (VariO:0136)
- transition (VariO:0313)
- pyrimidine transition (VariO:0314)
- purine transition (VariO:0315)
- not changed (VariO:0140)
- DNA deletion (VariO:0141)
- DNA insertion (VariO:0142)
- DNA indel (VariO:0143)
- DNA inversion (VariO:0145)
- DNA translocation (VariO:0144)
- transversion (VariO:0316)
VariO/Protein: variation ontology annotation at protein level
All options:
- protein truncation (VariO:0015)
- sequence retaining amino acid deletion (VariO:0016)
- nonsynonymous variation (VariO:0017)
- amino acid insertion (VariO:0018)
- amphigoric amino acid insertion (VariO:0019)
- sequence retaining amino acid insertion (VariO:0020)
- amino acid substitution (VariO:0021)
- amino acid indel (VariO:0022)
- amphigoric amino acid indel (VariO:0023)
- missing protein (VariO:0240)
- sequence retaining amino acid indel (VariO:0029)
- alternatively initiated protein (VariO:0443)
- artificial protein variation (VariO:0246)
- mistranslated protein (VariO:0330)
- protein structural inheritance (VariO:0026)
- epigenetic protein variation (VariO:0025)
- post translational modification (VariO:0028)
- proteinaceous infection (VariO:0027)
VariO/RNA: variation ontology annotation at RNA level
All options:
- RNA substitution (VariO:0312)
- transition (VariO:0313)
- pyrimidine transition (VariO:0314)
- purine transition (VariO:0315)
- transversion (VariO:0316)
- missense variation (VariO:0308)
- initiation codon change (VariO:0317)
- termination codon change (VariO:0309)
- nonsense variation (VariO:0310)
- silent variation (VariO:0318)
- RNA deletion (VariO:0319)
- in-frame deletion (VariO:0320)
- out-of-frame deletion (VariO:0321)
- RNA insertion (VariO:0326)
- in-frame insertion (VariO:0332)
- out-of-frame insertion (VariO:0327)
- RNA indel (VariO:0311)
- in-frame indel (VariO:0030)
- out-of-frame indel (VariO:0031)
- effect on RNA splicing (VariO:0362)
- intron gain (VariO:0364)
- RNA splicing change (VariO:0334)
- exon loss (VariO:0381)
- missing RNA (VariO:0245)
- unsense variation (VariO:0514)
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.
Haplotype: haplotype on which variant was found
RNA change: description of variant at RNA level (following HGVS recommendations).
- r.123c>u
- r.? = unknown
- r.(?) = RNA not analysed but probably transcribed copy of DNA variant
- r.spl? = RNA not analysed but variant probably affects splicing
- r.(spl?) = RNA not analysed but variant may affect splicing
- r.0? = change expected to abolish transcription
Protein: description of variant at protein level (following HGVS recommendations).
- p.(Arg345Pro) = change predicted from DNA (RNA not analysed)
- p.Arg345Pro = change derived from RNA analysis
- p.? = unknown effect
- p.0? = probably no protein produced
P-domain: region/domain protein affected
Exon_old: exon number according to older numbering
Function/GVS: functional annotation of position based on the Genome Variation Server
All options:
- intergenic
- 5 flank = near gene 5
- 5'UTR
- coding
- coding near splice
- coding synonymous
- coding synonymous near splice
- codingComplex
- codingComplex near splice
- frameshift
- frameshift near splice
- missense
- missense near splice
- 5' splice
- intron
- 3' splice
- stop gained
- stop gained near splice
- stop lost
- stop lost near splice
- 3'UTR
- 3 flank = near gene 3
Predict/AGVGD: Align GVGD score; C0, C15, C25, C35, C45, C55 or C65
Predict/MutationTaster: Mutation Taster prediction variant; disease causing, polymorphism
Predict/SIFT: SIFT predicted effect of variant
Predicted: predicted consequence of variant (RNA/protein level)
All options:
- missense
- nonsense
- frameshift
- no-stop
- silent
- splicing affected
- splicing affected, exon skipped
- splicing affected?
- deletion
- deletion, small
- deletion, large
- deletion, exon
- deletion, multi exon
- duplication
- duplication, small
- duplication, large
- insertion
- insertion, small
- insertion, large
- delins = insertion/deletion
- conversion
- other/complex
Type/DNA: type of variant at DNA level. NOTE: can be derived automatically from the variant description (for all levels)
All options:
- substitution
- deletion
- deletion, small
- deletion, large
- duplication
- duplication, small
- duplication, large
- insertion
- insertion, small
- insertion, large
- delins = insertion/deletion
- inversion
- conversion
- transposition
- translocation
- other/complex
CpG: Variation occurs in CpG dinucleotide; number is the position in the codon
Enzyme activity: activity variant enzym
mRNA level: Level of transcribed mRNA present in peripheral blood mononuclear cells. The level is indicated in relative terms as normal/(much) increased/(much) reduced/absent.
Predict-BioInf: predicted effect of variant using bioinformatic analysis tools (e.g. AGVGD, CADD, conservation, Grantham, MutationTaster, PolyPhen, REVEL, SIFT, splicing, etc.)
Legacy protein change: description of variant at protein level using a traditional (legacy) numbering system.
Protein level: Level of translated protein in peripheral blood mononuclear cells. The level is indicated in relative terms as normal/(much) increased/(much) reduced/absent.
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