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.
Reported : The number of times this variant has been reported in the database.
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
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%)
Effect
Reported
Exon
DNA change (cDNA)
RNA change
Protein
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
Owner
+/.
3
_1_15_
c.(?_-181)_(*220_?)del
r.0
p.0
-
pathogenic
g.(?_49834551)_(49857096_?)del
g.(?_50069896)_(50092439_?)del
g.50069896_50075809del
-
CLCN5_000000
whole gene deletion, breakpoints not characterized
PubMed: Mansour-Hendili 2015
-
-
Germline, Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
+/.
3
_1_15_
c.-382_*7016{0}
r.0
p.0
-
pathogenic
g.(?_49834580)_(49856877_?)del
-
whole gene deletion
-
CLCN5_000000
-
PubMed: Akuta 1997 , PubMed: Lloyd 1996 , PubMed: Sekine 2014
-
-
Germline, Unknown
yes
-
-
-
-
Johan den Dunnen , Rosa Vargas-Poussou
?/.
4
-
c.-205+33dup
r.(=)
p.(=)
-
VUS
g.49687435dup
-
-
-
chrX_001623, chrX_002491
-
-
-
-
Germline
-
-
-
-
-
Yu Sun
?/.
1
-
c.-205+214T>C
r.(=)
p.(=)
-
VUS
g.49687616T>C
-
-
-
chrX_001636
-
-
-
-
Germline
-
-
-
-
-
Yu Sun
+/.
1
11
c.?
r.(?)
p.?
-
pathogenic
g.(?)
-
Val363fs
-
CLCN5_000000
-
PubMed: Cramer 2014
-
-
Unknown
-
-
-
-
-
Rosa Vargas-Poussou
?/.
1
-
c.97A>G
r.(?)
p.(Ile33Val)
-
VUS
g.49807005A>G
g.50042396A>G
CLCN5(NM_001127899.3):c.97A>G (p.I33V)
-
CLCN5_000134
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Rotterdam
?/.
1
-
c.147A>C
r.(?)
p.(Leu49Phe)
-
VUS
g.49807055A>C
-
CLCN5(NM_001127899.3):c.147A>C (p.L49F)
-
CLCN5_000163
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Rotterdam
+/.
1
-
c.164-2260G>A
r.spl?
p.(=)
-
pathogenic
g.49832274G>A
g.50067619G>A
-480G>A
-
CLCN5_000095
not in 471 control chromosomes
PubMed: Tosetto 2009
-
-
Unknown
-
-
-
-
-
Johan den Dunnen
+?/.
1
-
c.164-433G>A
r.(?)
p.(=)
-
likely pathogenic
g.49834101G>A
g.50069446G>A
-
-
CLCN5_000116
-
-
-
-
Unknown
-
-
-
-
-
Rosa Vargas-Poussou
-?/.
1
-
c.164-140T>C
r.(=)
p.(=)
-
likely benign
g.49834394T>C
g.50069739T>C
CLCN5(NM_001282163.1):c.8T>C (p.L3P)
-
CLCN5_000120
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Rotterdam
-?/.
1
-
c.164-6A>T
r.(=)
p.(=)
-
likely benign
g.49834528A>T
-
CLCN5(NM_001127899.3):c.164-6A>T
-
CLCN5_000164
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Rotterdam
-?/.
1
-
c.167A>G
r.(?)
p.(Asp56Gly)
-
likely benign
g.49834537A>G
-
CLCN5(NM_001127899.3):c.167A>G (p.D56G)
-
CLCN5_000165
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Rotterdam
-?/.
1
-
c.168C>A
r.(?)
p.(Asp56Glu)
-
likely benign
g.49834538C>A
-
CLCN5(NM_001127899.2):c.168C>A (p.(Asp56Glu))
-
CLCN5_000180
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Leiden
+/.
1
-
c.(?_211)_(315+1_316-1)del
r.0?
p.0?
-
pathogenic
g.(?_49834581)_(49834686_49837143)del
g.(?_50069926)_(50070031_50072488)del
NM_000084.2:c.1-?_105+?del, delex2
-
CLCN5_000008
-
PubMed: Mansour-Hendili 2015
-
-
Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
+/.
1
-
c.(?_211)_(415+1_416-1)del
r.0?
p.0?
-
pathogenic
g.(?_49834580)_(49837244_49840449)del
g.(?_50069926)_(50072589_50075794)del
NM_000084.2:c.1-?_205+?del, del ex2-3
-
CLCN5_000117
-
PubMed: Mansour-Hendili 2015
-
-
Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
+/.
1
-
c.(?_211)_(603+1_604-1)del
r.0?
p.0?
-
pathogenic
g.(?_49834581)_(49840638_49845250)del
g.(?_50069926)_(50075983_50080593)del
NM_000084.2:c.1-?_393+?del, del ex2-4
-
CLCN5_000009
-
PubMed: Mansour-Hendili 2015
-
-
Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
+/.
1
-
c.221del
r.(?)
p.(Leu74Trpfs*8)
-
pathogenic
g.49834591del
-
CLCN5(NM_000084.5):c.11delT (p.L4Wfs*8)
-
CLCN5_000179
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Utrecht
?/.
1
-
c.252T>G
r.(?)
p.(Tyr84Ter)
-
VUS
g.49834622T>G
g.50069967T>G
CLCN5(NM_001127899.3):c.252T>G (p.Y84*)
-
CLCN5_000135
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Rotterdam
?/.
1
-
c.262A>C
r.(?)
p.(Asn88His)
-
VUS
g.49834632A>C
-
-
-
CLCN5_000181
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Nijmegen
+/., +?/.
9
-
c.292C>T
r.(?)
p.(Arg98*), p.(Arg98Ter)
-
likely pathogenic, pathogenic
g.49834662C>T
g.50070007C>T
NM_000084.2:c.82C>T
-
CLCN5_000006
-
PubMed: Akuta 1997 , PubMed: Cramer 2014 , PubMed: Dinour 2009 , PubMed: Hoopes 1998 , PubMed: Sekine 2014 , 2 more items
-
-
Germline, Germline/De novo (untested), Unknown
-
-
-
-
-
Rosa Vargas-Poussou
+/.
1
-
c.297_298insAAC
r.(?)
p.(Asp99_Arg100insAsn)
-
pathogenic
g.49834667_49834668insAAC
g.50070012_50070013insAAC
AAC in frame 30:H
-
CLCN5_000075
-
PubMed: Lloyd 1997
-
-
Germline
-
-
-
-
-
Johan den Dunnen
+?/.
1
-
c.302del
r.(?)
p.(Asp101Valfs*17)
-
likely pathogenic
g.49834672del
g.50070017del
-
-
CLCN5_000101
-
PubMed: Fervenza 2013
-
-
Unknown
-
-
-
-
-
Rosa Vargas-Poussou
+/.
1
-
c.310C>T
r.(?)
p.(Arg104Ter)
-
NA
g.49834680C>T
g.50070025C>T
C391T
-
CLCN5_000186
-
PubMed: Ludwig 2006
-
-
Germline/De novo (untested)
-
-
-
-
-
Johan den Dunnen
+/., +?/.
2
2i
c.315G>A
r.spl?, r.[315G>A,315_316ins315+1_315+23]
p.(?), p.Ile106ValfsTer20
-
likely pathogenic, NA
g.49834685G>A
g.50070030G>A
NM_000084.2:c.105G>A (Glu353Glu)
-
CLCN5_000010
effect on RNA studied using mini-gene splicing assay, splicing effect
PubMed: Inoue 2020 , PubMed: Mansour-Hendili 2015
-
-
Germline, In vitro (cloned)
-
-
-
-
-
Johan den Dunnen , Rosa Vargas-Poussou
+/.
1
2i
c.315+5G>C
r.315_316ins[GTAAAC;315+6_315+23]
p.Ile106ValfsTer20
-
NA
g.49834690G>C
g.50070035G>C
-
-
CLCN5_000184
effect on RNA studied using mini-gene splicing assay
PubMed: Inoue 2020
-
-
In vitro (cloned)
-
-
-
-
-
Johan den Dunnen
+?/., -/., -?/.
3
2i
c.316-17T>G
r.(=), r.315_316=, r.c.316-135_316ins[316-134_316-18;G;316-16_316-1]
p.(=), p.=, p.?
-
benign, likely pathogenic, NA
g.49837127T>G
g.50072472T>G
IVS2–17T>G
-
CLCN5_000107
effect on RNA studied using mini-gene splicing assay, VKGL data sharing initiative Nederland
PubMed: Forino 2004 , PubMed: Inoue 2020
-
-
CLASSIFICATION record, De novo, In vitro (cloned)
-
-
-
-
-
Johan den Dunnen , Rosa Vargas-Poussou , VKGL-NL_Nijmegen
+/.
1
-
c.318del
r.(?)
p.(Thr107Profs*11)
-
pathogenic
g.49837146del
-
CLCN5(NM_000084.5):c.108delT (p.T37Pfs*11)
-
CLCN5_000158
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_VUmc
?/.
1
-
c.332A>G
r.(?)
p.(Lys111Arg)
-
VUS
g.49837160A>G
g.50072505A>G
CLCN5(NM_000084.2):c.122A>G (p.(Lys41Arg))
-
CLCN5_000121
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Leiden
+/.
2
-
c.344G>A
r.(?)
p.(Trp115Ter)
-
NA, pathogenic
g.49837172G>A
g.50072517G>A
G425A, TGG>TAG W45X
-
CLCN5_000187
-
PubMed: Hoopes 2004 , PubMed: Ludwig 2006
-
-
Germline/De novo (untested)
-
-
-
-
-
Johan den Dunnen
+/.
1
-
c.376del
r.(?)
p.(Ser126ProfsTer5)
-
pathogenic
g.49837204del
g.50072549del
NM_000084.2:c.166del
-
CLCN5_000011
-
PubMed: Mansour-Hendili 2015
-
-
Germline
-
-
-
-
-
Rosa Vargas-Poussou
+/.
1
-
c.379G>C
r.(?)
p.(Gly127Arg)
-
pathogenic
g.49837207G>C
g.50072552G>C
-
-
CLCN5_000126
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Nijmegen
+/.
2
-
c.380G>T
r.(?)
p.(Gly127Val)
-
pathogenic
g.49837208G>T
g.50072553G>T
Gly57Val, Gly57Val (GGC>GTC)
-
CLCN5_000076
-
PubMed: Lloyd 1997 , PubMed: Schurman 1998 , OMIM:var0011
-
rs151340629
Germline
yes
-
MspI
-
-
Johan den Dunnen
+/.
1
-
c.383G>T
r.(?)
p.(Trp128Leu)
-
pathogenic
g.49837211G>T
g.50072556G>T
464G>T
-
CLCN5_000081
-
PubMed: Tosetto 2009
-
-
Germline
yes
-
-
-
-
Johan den Dunnen
-/., -?/., ?/.
3
-
c.416-6A>T
r.(=), r.(?)
p.(=)
-
benign, likely benign, VUS
g.49840444A>T
g.50075789A>T
CLCN5(NM_000084.2):c.206-6A>T (p.(=)), CLCN5(NM_000084.5):c.206-6A>T, NM_000084.2:c.206-6A>T
-
CLCN5_000108
VKGL data sharing initiative Nederland
PubMed: Mansour-Hendili 2015
-
rs6651602
CLASSIFICATION record, Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou , VKGL-NL_Leiden , VKGL-NL_Utrecht
+?/.
1
-
c.416-1G>C
r.spl
p.?
-
likely pathogenic
g.49840449G>C
g.50075794G>C
NM_000084.2:c.206-1G>C
-
CLCN5_000012
Loss of splice acceptor site
PubMed: Mansour-Hendili 2015
-
-
Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
-?/.
1
-
c.473G>A
r.(?)
p.(Gly158Asp)
-
NA
g.49840507G>A
g.50075852G>A
G554A
-
CLCN5_000188
-
PubMed: Ludwig 2006
-
-
Germline
yes
-
-
-
-
Johan den Dunnen
+/.
1
-
c.494G>A
r.(?)
p.(Trp165Ter)
-
NA
g.49840528G>A
g.50075873G>A
G575A
-
CLCN5_000189
-
PubMed: Ludwig 2006
-
-
Germline/De novo (untested)
-
-
-
-
-
Johan den Dunnen
+?/.
1
-
c.518G>A
r.(?)
p.(Trp173Ter)
-
likely pathogenic
g.49840552G>A
g.50075897G>A
NM_000084.2:c.308G>A
-
CLCN5_000013
-
PubMed: Mansour-Hendili 2015
-
-
Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
+?/.
1
-
c.519G>A
r.(?)
p.(Trp173Ter)
-
likely pathogenic
g.49840553G>A
g.50075898G>A
NM_000084.2:c.309G>A
-
CLCN5_000014
-
PubMed: Mansour-Hendili 2015
-
-
Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
-?/., ?/.
3
-
c.554A>G
r.(?)
p.(Lys185Arg)
-
likely benign, VUS
g.49840588A>G
g.50075933A>G
1 more item
-
CLCN5_000122
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Leiden , VKGL-NL_Rotterdam , VKGL-NL_Utrecht
+/.
1
-
c.594C>G
r.(?)
p.(Ser198Arg)
-
pathogenic
g.49840628C>G
g.50075973C>G
-
-
CLCN5_000002
found once, nonrecurrent change
PubMed: Tarpey 2009
-
-
Germline
-
1/208 cases
-
-
-
Lucy Raymond
+/.
1
7
c.603G>A
r.spl
p.?
-
pathogenic (recessive)
g.49840637G>A
g.50075982G>A
-
-
CLCN5_000190
ACMG PVS1, PM2, PP3, PP4
PubMed: Lyu 2026
-
-
Germline/De novo (untested)
-
-
-
-
-
Johan den Dunnen
+/.
2
4i
c.603+4A>G
r.416_613del, r.spl
p.?, p.Gly139_Phe204del
-
NA, pathogenic
g.49840641A>G
g.50075986A>G
IVS4+4A>G
-
CLCN5_000092
effect on RNA studied using mini-gene splicing assay
PubMed: Inoue 2020 , PubMed: Tosetto 2009
-
-
In vitro (cloned), Unknown
-
-
-
-
-
Johan den Dunnen
-?/.
1
-
c.603+6_603+7del
r.(=)
p.(=)
-
likely benign
g.49840643_49840644del
-
CLCN5(NM_001127899.3):c.603+6_603+7delAT
-
CLCN5_000152
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Rotterdam
?/.
2
-
c.604-110del
r.(=)
p.(=)
-
VUS
g.49845141del
g.50080484del
-
-
CLCN5_000097
-
-
-
-
Germline
-
-
-
-
-
Yu Sun
-?/.
1
-
c.604-8T>C
r.(=)
p.(=)
-
likely benign
g.49845243T>C
-
CLCN5(NM_000084.5):c.394-8T>C
-
CLCN5_000174
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Utrecht
+?/.
4
-
c.604-2A>G
r.spl
p.?
-
likely pathogenic
g.49845249A>G
g.50080592A>G
NM_000084.2:c.394-2A>G
-
CLCN5_000007
Loss of splice acceptor site
PubMed: Mansour-Hendili 2015 , PubMed: Sekine 2014 , PubMed: Zhu 2010
-
-
Germline, Germline/De novo (untested), Unknown
-
-
-
-
-
Rosa Vargas-Poussou
+/.
1
-
c.604-1G>C
r.spl?
p.?
-
pathogenic
g.49845250G>C
-
-
-
CLCN5_000153
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Nijmegen
+/.
1
4i_6i
c.(603+1_604-1)_(933+1_934-1)del
r.604_933del
p.Gly132_Glu241del
-
pathogenic
g.(49840638_49845250)_(49846505_49850636)del
-
2 kb deletion exons 5-6
-
CLCN5_000071
-
PubMed: Lloyd 1996
-
-
Germline
yes
-
-
-
-
Johan den Dunnen
+/.
1
-
c.613_614del
r.(?)
p.(Ala205LeufsTer37)
-
pathogenic
g.49845260_49845261del
g.50080603_50080604del
NM_000084.2:c.403_404del
-
CLCN5_000015
-
PubMed: Mansour-Hendili 2015
-
-
Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
?/.
1
-
c.617A>G
r.(?)
p.(Tyr206Cys)
-
VUS
g.49845264A>G
g.50080607A>G
CLCN5(NM_000084.2):c.407A>G (p.(Tyr136Cys))
-
CLCN5_000136
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Leiden
+/.
1
-
c.620dup
r.(?)
p.(Val208SerfsTer35)
-
pathogenic
g.49845267dup
g.50080610dup
NM_000084.2:c.410dup
-
CLCN5_000016
-
PubMed: Mansour-Hendili 2015
-
-
Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
-/.
1
-
c.636G>A
r.(?)
p.(Met212Ile)
-
benign
g.49845283G>A
-
CLCN5(NM_000084.5):c.426G>A (p.M142I)
-
CLCN5_000170
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Utrecht
-?/.
1
-
c.640G>A
r.(?)
p.(Val214Ile)
-
likely benign
g.49845287G>A
-
CLCN5(NM_001127899.3):c.640G>A (p.V214I)
-
CLCN5_000144
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Rotterdam
+?/.
1
-
c.648G>A
r.(?)
p.(Trp216Ter)
-
likely pathogenic
g.49845295G>A
g.50080638G>A
NM_000084.2:c.438G>A
-
CLCN5_000017
-
PubMed: Mansour-Hendili 2015
-
-
Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
+/.
1
-
c.726+1G>A
r.604_726del
p.Gly132_Glu172del
-
pathogenic
g.49845374G>A
g.50080717G>A
IVS5 gt>at
-
CLCN5_000070
-
PubMed: Lloyd 1996
-
-
Germline
yes
-
HphI
-
-
Johan den Dunnen
+/.
1
-
c.726+2T>G
r.604_726del
p.Gly132_Glu172del
-
pathogenic
g.49845375T>G
g.50080718T>G
IVS5 gt>gg
-
CLCN5_000069
-
PubMed: Lloyd 1996
-
-
Germline
yes
-
HphI
-
-
Johan den Dunnen
+?/.
1
-
c.726+5G>C
r.spl?
p.?
-
likely pathogenic
g.49845378G>C
g.50080721G>C
-
-
CLCN5_000137
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Nijmegen
+/., +?/.
2
5i
c.727-8A>G
r.spl, r.[726_727insCCTGCAG,727_758del,727_814del,727_933del]
p.?, p.[Ile243ProfsTer13,Ile243GlyfsTer5,Ile243CysfsTer5,Ile243_Glu311del]
-
likely pathogenic, NA
g.49846290A>G
g.50081633A>G
NM_000084.2:c.517-8A>G
-
CLCN5_000018
effect on RNA studied using mini-gene splicing assay
PubMed: Inoue 2020 , PubMed: Mansour-Hendili 2015
-
-
Germline, In vitro (cloned)
-
-
-
-
-
Johan den Dunnen , Rosa Vargas-Poussou
+/.
1
5i
c.727-3C>A
r.[727_758del,727_814del,727_933del]
p.[Ile243GlyfsTer5,Ile243CysfsTer5,Ile243_Glu311del]
-
NA
g.49846295C>A
g.50081638C>A
-
-
CLCN5_000191
effect on RNA studied using mini-gene splicing assay
PubMed: Inoue 2020
-
-
In vitro (cloned)
-
-
-
-
-
Johan den Dunnen
+/.
2
-
c.746G>A
r.(?)
p.(Gly249Asp)
-
pathogenic
g.49846317G>A
g.50081660G>A
NM_000084.2:c.536G>A
-
CLCN5_000019
-
PubMed: Grand 2009 , PubMed: Mansour-Hendili 2015
-
-
Germline, Unknown
-
-
-
-
-
Rosa Vargas-Poussou
+/.
1
-
c.784del
r.(?)
p.(Val262Leufs*15)
-
pathogenic
g.49846355del
g.50081698del
865delG
-
CLCN5_000082
-
PubMed: Tosetto 2009
-
-
Unknown
-
-
-
-
-
Johan den Dunnen
+/.
1
-
c.807_808dup
r.(?)
p.(Leu270ArgfsTer8)
-
pathogenic
g.49846378_49846379dup
g.50081721_50081722dup
NM_000084.2:c.597_598dup
-
CLCN5_000020
-
PubMed: Mansour-Hendili 2015
-
-
Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
+/.
1
-
c.809T>G
r.(?)
p.(Leu270Arg)
-
pathogenic
g.49846380T>G
g.50081723T>G
Leu200Arg (CTG>CGG)
-
CLCN5_000066
-
PubMed: Lloyd 1996 , OMIM:var0003
-
rs151340622
Germline
yes
-
AciI
-
-
Johan den Dunnen
+/.
2
-
c.818C>A
r.(?)
p.(Ser273*), p.(Ser273Ter)
-
pathogenic
g.49846389C>A
g.50081732C>A
NM_000084.2:c.608C>A
-
CLCN5_000021
-
PubMed: Blanchard 2008 , PubMed: Mansour-Hendili 2015
-
-
Germline, Unknown
-
-
-
-
-
Rosa Vargas-Poussou
+/.
4
-
c.818C>T
r.(?)
p.(Ser273Leu)
-
pathogenic
g.49846389C>T
g.50081732C>T
NM_000084.2:c.608C>T
-
CLCN5_000022
-
PubMed: Grand 2009 , PubMed: Mansour-Hendili 2015 , PubMed: Park 2014 , PubMed: Sekine 2014
-
-
Germline/De novo (untested), Unknown
-
-
-
-
-
Rosa Vargas-Poussou
-?/.
1
-
c.819=
r.(=)
p.(Ser273=)
-
likely benign
g.49846390G>A
-
CLCN5(NM_000084.5):c.609G>A (p.S203=)
-
CLCN5_000178
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Utrecht
+/.
4
-
c.845G>C
r.(?)
p.(Gly282Ala)
-
pathogenic
g.49846416G>C
g.50081759G>C
NM_000084.2:c.635G>C
-
CLCN5_000023
-
PubMed: Grand 2009 , PubMed: Mansour-Hendili 2015
-
-
Germline, Unknown
-
-
-
-
-
Rosa Vargas-Poussou
+/.
10
-
c.871T>C
r.(?)
p.(Cys291Arg)
-
NA, pathogenic
g.49846442T>C, g.49853406C>T
g.50081785T>C
NM_000084.2:c.661T>C, T952C, TGT>CGT C221R
-
CLCN5_000024, CLCN5_000041
1 more item
PubMed: Dinour 2009 , PubMed: Hoopes 2004 , PubMed: Li 2009 , PubMed: Ludwig 2005 , PubMed: Ludwig 2006 , 4 more items
-
-
Germline, Germline/De novo (untested), Unknown
-
-
-
-
-
Johan den Dunnen , Rosa Vargas-Poussou
+/.
1
-
c.873T>A
r.(?)
p.(Cys291Ter)
-
pathogenic
g.49846444T>A
g.50081787T>A
TGT>TGA C221X
-
CLCN5_000204
-
PubMed: Hoopes 2004
-
-
Germline/De novo (untested)
-
-
-
-
-
Johan den Dunnen
+/.
1
-
c.891_892del
r.(?)
p.(His297GlnfsTer9)
-
pathogenic
g.49846462_49846463del
g.50081805_50081806del
NM_000084.2:c.681_682del
-
CLCN5_000025
-
PubMed: Mansour-Hendili 2015
-
-
Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
?/.
1
-
c.902A>C
r.(?)
p.(Lys301Thr)
-
VUS
g.49846473A>C
-
-
-
CLCN5_000175
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Nijmegen
+?/.
1
-
c.902A>T
r.(?)
p.(Lys301Ile)
-
likely pathogenic
g.49846473A>T
g.50081816A>T
NM_000084.2:c.692A>T
-
CLCN5_000026
-
PubMed: Mansour-Hendili 2015
-
-
Germline
-
-
-
-
-
Rosa Vargas-Poussou
+/.
1
-
c.909del
r.(?)
p.(Lys304ArgfsTer20)
-
pathogenic
g.49846480del
g.50081823del
NM_000084.2:c.699del
-
CLCN5_000027
-
PubMed: Mansour-Hendili 2015
-
-
Germline
-
-
-
-
-
Rosa Vargas-Poussou
?/.
1
-
c.926G>A
r.(?)
p.(Arg309His)
-
VUS
g.49846497G>A
-
CLCN5(NM_001127899.3):c.926G>A (p.R309H)
-
CLCN5_000160
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Rotterdam
+?/.
1
-
c.926G>C
r.(?)
p.(Arg309Pro)
-
likely pathogenic
g.49846497G>C
g.50081840G>C
NM_000084.2:c.716G>C
-
CLCN5_000028
-
PubMed: Mansour-Hendili 2015
-
-
Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
+?/.
1
-
c.931G>T
r.(?)
p.(Glu311Ter)
-
likely pathogenic
g.49846502G>T
g.50081845G>T
NM_000084.2:c.721G>T
-
CLCN5_000029
-
PubMed: Mansour-Hendili 2015
-
-
Germline
-
-
-
-
-
Rosa Vargas-Poussou
+?/.
1
-
c.933+1G>A
r.spl?
p.?
-
likely pathogenic
g.49846505G>A
g.50081848G>A
-
-
CLCN5_000103
-
PubMed: Cramer 2014
-
-
Unknown
-
-
-
-
-
Rosa Vargas-Poussou
+/.
1
-
c.933+2T>C
r.0
p.0
-
pathogenic (recessive)
g.49846506T>C
g.50081849T>C
-
-
CLCN5_000119
-
PubMed: Ji 2014 , Journal: Ji 2014
-
-
Germline/De novo (untested)
-
-
-
-
-
Pieter Klap
?/.
1
-
c.934-35T>G
r.(?)
p.(=)
-
VUS
g.49850602T>G
g.50085945T>G
IVS6-35G
-
CLCN5_000109
-
-
-
-
Germline
-
-
-
-
-
Rosa Vargas-Poussou
+?/.
2
-
c.934-2A>G
r.spl
p.?
-
likely pathogenic
g.49850635A>G
g.50085978A>G
NM_000084.2:c.724-2A>G
-
CLCN5_000030
Loss of splice acceptor site
PubMed: Mansour-Hendili 2015
-
-
Germline, Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
+?/.
1
-
c.934-1G>A
r.spl
p.?
-
likely pathogenic
g.49850636G>A
g.50085979G>A
NM_000084.2:c.724-1G>A
-
CLCN5_000031
Loss of splice acceptor site
PubMed: Mansour-Hendili 2015
-
-
Germline
-
-
-
-
-
Rosa Vargas-Poussou
+/.
20
-
c.941C>T
r.(?)
p.(Ser314Leu)
-
pathogenic
g.49850644C>T
g.50085987C>T
C1022T, CLCN5(NM_000084.5):c.731C>T (p.S244L), NM_000084.2:c.731C>T, Ser244Leu (TCG>TTG), 2 more items
-
CLCN5_000005
functional analysis shows variant abolished anion conductance sequence, 1 more item
PubMed: Anglani 2006 , PubMed: Hoopes 1998 , PubMed: Hoopes 2004 , PubMed: Kelleher 1998 , 7 more items
-
rs151340626
CLASSIFICATION record, De novo, Germline, Germline/De novo (untested), Unknown
yes
-
-
-
-
Johan den Dunnen , Rosa Vargas-Poussou , VKGL-NL_Utrecht , VKGL-NL_Nijmegen
-?/.
1
-
c.942G>A
r.(?)
p.(Ser314=)
-
likely benign
g.49850645G>A
-
CLCN5(NM_001127899.3):c.942G>A (p.S314=)
-
CLCN5_000161
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Rotterdam
+?/.
1
-
c.958G>C
r.(?)
p.(Gly320Arg)
-
likely pathogenic
g.49850661G>C
g.50086004G>C
NM_000084.2:c.748G>C
-
CLCN5_000032
-
PubMed: Mansour-Hendili 2015
-
-
Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
+?/.
1
-
c.983C>G
r.(?)
p.(Pro328Arg)
-
likely pathogenic
g.49850686C>G
g.50086029C>G
CLCN5(NM_001127899.4):c.983C>G (p.P328R)
-
CLCN5_000141
VKGL data sharing initiative Nederland
-
-
-
CLASSIFICATION record
-
-
-
-
-
VKGL-NL_Groningen
+/.
1
-
c.983delinsGGAA
r.(?)
p.(Pro328delinsArgAsn)
-
pathogenic
g.49850686delinsGGAA
g.50086029delinsGGAA
NM_000084.2:c.773delinsGGAA
-
CLCN5_000033
-
PubMed: Mansour-Hendili 2015
-
-
Germline
-
-
-
-
-
Rosa Vargas-Poussou
+/.
1
-
c.989G>T
r.(?)
p.(Gly330Val)
-
pathogenic
g.49850692G>T
g.50086035G>T
1070G>Y (Gly260Val)
-
CLCN5_000080
-
PubMed: Tosetto 2006 , OMIM:var0013
-
rs151340630
Germline
-
1/25 case
-
-
-
Johan den Dunnen
+/.
1
-
c.990del
r.(?)
p.(Gly331GlufsTer98)
-
pathogenic
g.49850693del
g.50086036del
NM_000084.2:c.780del
-
CLCN5_000034
-
PubMed: Mansour-Hendili 2015
-
-
Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
+/.
2
-
c.991G>A
r.(?)
p.(Gly331Arg)
-
pathogenic, pathogenic (recessive)
g.49850694G>A
g.50086037G>A
1072G>A, NM_000084.2:c.781G>A
-
CLCN5_000083
-
PubMed: Mansour-Hendili 2015 , PubMed: Tosetto 2009
-
-
Germline/De novo (untested), Unknown
-
-
-
-
-
Johan den Dunnen
+/+
1
-
c.992G>A
r.992G>A
p.(Gly331Glu)
ACMG
pathogenic
g.49850695G>A
g.50086038G>A
-
-
CLCN5_000147
-
PubMed: Bogdanovic 2010
-
-
De novo
-
-
-
-
-
Rosa Vargas-Poussou
+/.
1
-
c.992_994del
r.(?)
p.(Gly331del)
-
pathogenic
g.49850695_49850697del
g.50086038_50086040del
1072_1074del
-
CLCN5_000084
-
PubMed: Tosetto 2009
-
-
Unknown
-
-
-
-
-
Johan den Dunnen
+?/.
1
-
c.993_1000dup
r.(?)
p.(Phe334*)
-
likely pathogenic
g.49850696_49850703dup
g.50086039_50086046dup
CLCN5 (NM_001127899.1):c.992_993insAGTATTAT(p.F334Xfs*1)
-
CLCN5_000169
different transcript: CLCN5 (NM_001127899.1):c.992_993insAGTATTAT(p.F334Xfs*1)
PubMed: Sun 2018
-
-
Germline/De novo (untested)
?
136
-
-
-
LOVD
+?/+?
1
-
c.1006C>G
r.1006c>g
p.(Leu336Val)
ACMG
likely pathogenic
g.49850709C>G
-
-
-
CLCN5_000148
-
PubMed: Sekine 2014
-
-
Germline
-
-
-
-
-
Rosa Vargas-Poussou
./.
1
-
c.1009G>A
r.1009g>a
p.(Glu337Lys)
ACMG
likely pathogenic
g.49850712G>A
-
-
-
CLCN5_000149
-
PubMed: Ashton 2018
-
-
Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
+/.
1
-
c.1010A>C
r.(?)
p.(Glu337Ala)
-
pathogenic
g.49850713A>C
g.50086056A>C
GAA>GCA E267A
-
CLCN5_000205
-
PubMed: Hoopes 2004
-
-
Germline/De novo (untested)
-
-
-
-
-
Johan den Dunnen
+?/.
1
-
c.1011A>C
r.(?)
p.(Glu337Asp)
-
likely pathogenic
g.49850714A>C
g.50086057A>C
NM_000084.2:c.801A>C
-
CLCN5_000035
-
PubMed: Mansour-Hendili 2015
-
-
Germline
-
-
-
-
-
Rosa Vargas-Poussou
+?/.
1
-
c.1018A>G
r.(1018A>G)
p.(Ser340Gly)
-
likely pathogenic
g.49850988A>G
g.50086331A>G
AGC>GGC S270G
-
CLCN5_000150
-
PubMed: Hoopes 2004
-
-
Germline/De novo (untested)
-
-
-
-
-
Rosa Vargas-Poussou
+?/.
1
-
c.1019G>A
r.(?)
p.(Ser340Asn)
-
likely pathogenic
g.49850989G>A
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CLCN5(NM_000084.5):c.809G>A (p.S270N)
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CLCN5_000171
VKGL data sharing initiative Nederland
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CLASSIFICATION record
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VKGL-NL_Utrecht
+?/.
1
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c.1020C>G
r.(?)
p.(Ser340Arg)
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likely pathogenic
g.49850990C>G
g.50086333C>G
NM_000084.2:c.810C>G
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CLCN5_000036
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PubMed: Mansour-Hendili 2015
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Germline
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Rosa Vargas-Poussou