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
Predict/MutationTaster: Mutation Taster prediction variant; disease causing, polymorphism
P-domain: region/domain protein affected
Predict/PolyPhen: PolyPhen predicted effect of variant; benign, possibly damaging, probably damaging, unknown (no prediction)
Predict/SIFT: SIFT predicted effect of variant
Conservation: conservation, conservation score, (species)
Predict/Splice: splice prediction
Enzyme activity: activity variant enzym
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)
- 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%)

 Effect
|

 Exon
|

 DNA change (cDNA)
|

 RNA change
|

 Protein
|

 Predict/MutationTaster
|

 P-domain
|

 Predict/PolyPhen
|

 Predict/SIFT
|

 Conservation
|

 Predict/Splice
|

 Enzyme activity
|

 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
|
+/+ |
4 |
c.[649_654dup;657_661del] |
r.(?) |
p.([Asp217_Gly218dup; Gly219fs*7]) |
- |
LDL-receptor class A5 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.[11216231_11216236dup;11216239_11216243del] |
- |
[D196_G197dup;G198fsX7] |
- |
LDLR_000370 |
predicted trucated protein; 6bp duplication (GATGGT) & 5bp deletion (CCCCG) |
PubMed: Giesel 1995 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_2i |
c.-1823_190+566del |
r.(?) |
p.0? |
- |
Promoter - exon 2 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11198402_11211587del |
g.11087726_11100911del |
- |
- |
LDLR_000005 |
predicted no protein; Deletion of exons 1 & 2; May be the same as c.1-?_190+?del |
PubMed: Goldmann 2010 |
- |
- |
Germline |
- |
1/37 patients with LDLR mutation. 1/1945 FH patients. Variant not present in controls |
- |
0 |
- |
Sarah Leigh |
+/. |
_1_1i |
c.-1818_67+1091delinsTTC |
r.0? |
p.0? |
- |
- |
- |
- |
- |
- |
- |
- |
pathogenic (dominant) |
g.11198407_11201382delinsTTC |
g.11087731_11090706delinsTTC |
11198406_11201384del, insTTCG |
- |
LDLR_002172 |
2977 del exon 1 |
PubMed: Wong 2019, Journal: Wong 2019 |
- |
- |
Germline |
yes |
- |
- |
0 |
- |
Karen HY Wong |
?/. |
- |
c.-283G>C |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
VUS |
g.11199942G>C |
- |
LDLR(NM_000527.4):c.-283G>C |
- |
LDLR_002298 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
VKGL-NL_AMC |
-?/-? |
_1 |
c.-268G>T |
r.(=) |
p.? |
- |
FP2 cis acting regulatory element |
- |
- |
7/8 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
Transient transfection in HepG2 cells demonstrated |
ACGS |
likely benign |
g.11199957G>T |
g.11089281G>T |
- |
- |
LDLR_000374 |
Hobb's numbering -175. Probably rare African non-disease causing variant. Found in FH and normal, may contribute to FH when present with other FH alleles (c.1222G>A, p.E408K) |
PubMed: Scholtz 1999 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
-?/-? |
_1 |
c.-268G>T |
r.(=) |
p.? |
- |
FP2 cis acting regulatory element |
- |
- |
7/8 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
limited effect on LDLR activity |
ACGS |
likely benign |
g.11199957G>T |
g.11089281G>T |
- |
- |
LDLR_000374 |
- |
PubMed: Whittall 2002 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
-?/. |
- |
c.-268G>T |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
likely benign |
g.11199957G>T |
g.11089281G>T |
LDLR(NM_000527.4):c.-268G>T |
- |
LDLR_000374 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
VKGL-NL_AMC |
?/? |
_1 |
c.-221_-220insA |
r.(=) |
p.? |
- |
FP1 cis acting regulatory element |
- |
- |
- |
- |
- |
ACGS |
VUS |
g.11200005dup |
g.11089329dup |
- |
- |
LDLR_000950 |
- |
PubMed: Bodamer 2002 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
-?/-? |
_1 |
c.-217C>T |
r.(=) |
p.? |
- |
FP1 cis acting regulatory element |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
160% luciferase activity compared to wt {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
ACGS |
likely benign |
g.11200008C>T |
g.11089332C>T |
- |
- |
LDLR_000015 |
predicted enhanced transcription; Hobb's numbering -124; Within 2bp of cis-acting regulatory element FP1; Found with c.-149C>T (Hobb's numbering -59) in normal son of proband for c.-149C>T |
PubMed: Scholtz 1999 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
-?/? |
_1 |
c.-217C>T |
r.(=) |
p.? |
- |
FP1 cis acting regulatory element |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
160% luciferase activity compared to wt {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
ACGS |
likely benign |
g.11200008C>T |
g.11089332C>T |
IVS1-217C>T |
- |
LDLR_000015 |
predicted enhanced transcription; Hobb's numbering -124; Within 2bp of cis-acting regulatory element FP1; Found on same allele as c.2041T>G, p.(Cys681Gly); increased expression of this pathogenic variant under the influence of c.-217C>T may explain the Hmz phenotype of this patient. |
PubMed: Snozek 2009 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
-?/. |
- |
c.-217C>T |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
likely benign |
g.11200008C>T |
- |
LDLR(NM_000527.4):c.-217C>T |
- |
LDLR_000015 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
VKGL-NL_AMC |
-?/? |
_1 |
c.-215A>G |
r.(=) |
p.? |
- |
FP1 cis acting regulatory element |
- |
- |
11/12 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
100% luciferase activity compared to wt {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
ACGS |
likely benign |
g.11200010A>G |
g.11089334A>G |
- |
- |
LDLR_000006 |
prediction no effect on transcription |
PubMed: Usifo 2012 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
-?/-? |
_1 |
c.-208A>T |
r.(=) |
p.? |
- |
SREBP1/FP1 |
- |
- |
12/12 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
100% of wt trascriptional activity (luciferase assay). |
ACGS |
likely benign |
g.11200017A>T |
g.11089341A>T |
- |
- |
LDLR_001268 |
prediction no effect on transcription |
PubMed: De Castro-Oros 2011 |
- |
- |
Germline |
- |
0.06 in this study |
- |
0 |
- |
Sarah Leigh |
?/? |
_1 |
c.-206C>T |
r.(=) |
p.? |
- |
SREBP1/FP1 |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
not tested |
ACGS |
VUS |
g.11200019C>T |
g.11089343C>T |
- |
- |
LDLR_001010 |
- |
PubMed: Lind 2002 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
?/? |
_1 |
c.-193_-186delinsTG |
r.(=) |
p.? |
- |
SREBP1 binding site |
- |
- |
- |
- |
not tested |
ACGS |
VUS |
g.11200032_11200039delinsTG |
g.11089356_11089363delinsTG |
- |
- |
LDLR_001024 |
- |
PubMed: Fouchier 2005 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
?/? |
_1 |
c.-188C>T |
r.(=) |
p.? |
- |
SREBP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
not tested |
ACGS |
VUS |
g.11200037C>T |
g.11089361C>T |
- |
- |
LDLR_001023 |
- |
PubMed: Fouchier 2005 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/. |
- |
c.-187C>T |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
likely pathogenic |
g.11200038C>T |
g.11089362C>T |
LDLR(NM_000527.4):c.-187C>T |
- |
LDLR_002180 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
VKGL-NL_AMC |
+/+ |
_1_1i |
c.(?_-187)_(67+1_68-1)del |
r.(?) |
p.0? |
- |
promotor & exon 1 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11200292del |
- |
c.-187-?_67+?del |
- |
LDLR_000007 |
predicted no protein; 13kb deletion of promotor & exon 1; Predicted to be pathogenic according to criteria set by Huijgen et al European Heart Journal (2012) 33, 2325–2330.
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Fouchier 2005 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_1i |
c.(?_-187)_(67+1_68-1)del |
r.(?) |
p.0? |
- |
Promotor - exon 1 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11200292del |
- |
c.-187-?_67+?del, FH Valencia-5 |
- |
LDLR_000007 |
predicted no protein; 6.8kb deletion of promotor & exon 1; Similar to FH Denver-1 (6kb deletion of promotor & exon 1); No mRNA
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Chaves 2001 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_1i |
c.(?_-187)_(67+1_68-1)del |
r.(?) |
p.0? |
- |
Promotor - exon 1 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11200292del |
- |
c.-187-?_67+?del |
- |
LDLR_000007 |
predicted no protein; 13kb deletion of exon 1
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Fouchier 2005 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_1i |
c.(?_-187)_(67+1_68-1)del |
r.(?) |
p.0? |
- |
Promotor - exon 1 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11200292del |
- |
c.-187-?_67+?del |
- |
LDLR_000007 |
predicted no protein; Deletion of promoter & exon 1; Found in one proband
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Tichy 2012 |
- |
- |
Germline |
- |
0.19 in this study |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_1i |
c.(?_-187)_(67+1_68-1)del |
r.(?) |
p.0? |
- |
Promotor - exon 1 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11200292del |
- |
c.-187-?_67+?del |
- |
LDLR_000007 |
predicted no protein; Deletion of exon 1; No details given of size, could be the same as other exon 1 deletions.
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Koeijvoets 2005 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_1i |
c.(?_-187)_(67+1_68-1)del |
r.(?) |
p.0? |
- |
Promoter - exon 1 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11200292del |
- |
c.-187-?_67+?del |
- |
LDLR_000007 |
predicted no protein; 9325bp deletion of promotor & exon 1 (see original paper for genomic breakpoints); Not the same as FH French Canadian-1
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Nissen 2006 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_1i |
c.(?_-187)_(67+1_68-1)del |
r.(?) |
p.0? |
- |
Promotor - exon 1 |
- |
- |
- |
- |
<2% LDLR activity when Htz with unknown FH allele |
ACGS |
pathogenic |
g.11200038_11200292del |
- |
c.-187-?_67+?del, FH Denver-1 |
- |
LDLR_000007 |
predicted no protein; Deletion of promotor & exon 1 (6kb); No detectable mRNA
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Hobbs 1988 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_1i |
c.(?_-187)_(67+1_68-1)del |
r.(?) |
p.0? |
- |
Promotor - exon 1 |
- |
- |
- |
- |
<2% LDLR activity in Hmz |
ACGS |
pathogenic |
g.11200038_11200292del |
- |
c.-187-?_67+?del, FH French Canadian-1 |
- |
LDLR_000007 |
predicted no protein; Deletion of promotor & exon 1 (>10kb); Found in 60% French Canadian FH
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Hobbs 1987 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_1i |
c.(?_-187)_(67+1_68-1)del |
r.(?) |
p.0? |
- |
Promotor - exon 1 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11200292del |
- |
c.-187-?_67+?del |
- |
LDLR_000007 |
predicted no protein; Deletion of promotor & exon 1, size of deletion not stated; Reported in 2 probands but may be different deletions in each.
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Marduel 2010 |
- |
- |
Germline |
- |
NA |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_1i |
c.(?_-187)_(67+1_68-1)del |
r.(?) |
p.0? |
- |
Promotor - exon 1 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11200292del |
- |
c.-187-?_67+?del |
- |
LDLR_000007 |
predicted no protein; Deletion >30 kb upstream of promotor & exon 1
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Sharifi 2016 |
- |
- |
Germline |
- |
NA |
- |
0 |
- |
Sarah Leigh |
+?/+? |
_1_1i |
c.(?_-187)_(67+1_68-1)dup |
r.(?) |
p.0? |
- |
Promotor - exon 1 |
- |
- |
- |
- |
- |
ACGS |
likely pathogenic |
g.11200038_11200292dup |
- |
c.-187-?_67+?dup |
- |
LDLR_001273 |
predicted no protein; Duplication of promotor & exon 1
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Sharifi 2016 |
- |
- |
Germline |
- |
NA |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_2i |
c.(?_-187)_(190+1_191-1)del |
r.(?) |
p.0? |
- |
Promotor - exon 2 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11211022del |
- |
c.-187-?_190+?del |
- |
LDLR_000008 |
predicted no protein; Deletion of exons 1 & 2
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Chmara 2010 |
- |
- |
Germline |
- |
4/169 patients with LDLR mutation. 4/378 FH patients. Variant not present in Normal Non FH patients |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_2i |
c.(?_-187)_(190+1_191-1)del |
r.(?) |
p.0? |
- |
Promotor - exon 2 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11211022del |
- |
c.-187-?_190+?del |
- |
LDLR_000008 |
predicted no protein; 18kb deletion of promotor - exon 2; Similar to FH Siracusa (20kb deletion of promotor - exon 2)
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Chaves 2001 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_2i |
c.(?_-187)_(190+1_191-1)del |
r.(?) |
p.0? |
- |
Promotor - exon 2 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11211022del |
- |
c.-187-?_190+?del |
- |
LDLR_000008 |
predicted no protein; Deletion of exons 1-2; No details given of size could be the same as other deletions.
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Koeijvoets 2005 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_2i |
c.(?_-187)_(190+1_191-1)del |
r.(?) |
p.0? |
- |
Promotor - exon 2 |
- |
- |
- |
- |
45% LDLR activity in Htz fibroblasts |
ACGS |
pathogenic |
g.11200038_11211022del |
- |
c.-187-?_190+?del |
- |
LDLR_000008 |
predicted no protein; 20kb deletion of promotor and exons 1-2; Similar to FH Valencia-1 (18kb deletion of prom-exon2)
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Garuti 1996 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_6i |
c.(?_-187)_(940+1_941-1)del |
r.(?) |
p.0? |
- |
Promoter - exon 6 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11218191del |
- |
c.-187-?_940+?del, FH Bologna-1 |
- |
LDLR_001274 |
predicted no protein; >10kb deletion of promotor & exons 1-6
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Sun 1992 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_6i |
c.(?_-187)_(940+1_941-1)del |
r.(?) |
p.0? |
- |
Promoter - exon 6 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11218191del |
- |
c.-187-?_940+?del, FH Bari-3 |
- |
LDLR_001274 |
predicted no protein; 24kb deletion the promotor - exon 6
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Bertolini 2000 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_6i |
c.(?_-187)_(940+1_941-1)del |
r.(?) |
p.0? |
- |
Promoter - exon 6 |
- |
- |
- |
- |
40-50% LDLR activity in Htz |
ACGS |
pathogenic |
g.11200038_11218191del |
- |
c.-187-?_940+?del, FH Bologna-1 |
- |
LDLR_001274 |
predicted no protein; >25kb deletion of promotor & exons 1-6
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Lelli 1991 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_7i |
c.(?_-187)_(1060+1_1061-1)del |
r.(?) |
p.0? |
- |
Promoter - exon 7 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11221448del |
- |
c.-187-?_1060+?del |
- |
LDLR_001271 |
predicted no protein; Deletion of promoter - exon 7; Found in 1 proband, segregates with FH in 2 affected relatives and not in 2 unaffected relatives
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Marduel 2010 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_8i |
c.(?_-187)_(1186+1_1187-1)del |
r.(?) |
p.0? |
- |
Promoter - exon 8 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11222316del |
- |
c.-187-?_1186+?del |
- |
LDLR_001091 |
predicted no protein; 23kb deletion of promotor and exons 1-8
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Fouchier 2005 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_12i |
c.(?_-187)_(1845+1_1846-1)del |
r.(?) |
p.0? |
- |
Promoter - exon 12 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11227675del |
- |
c.-187-?_1845+?del |
- |
LDLR_001167 |
predicted no protein; Deletion of exons 1-12
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Shin 2015 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_14i |
c.(?_-187)_(2140+1_2141-1)del |
r.(?) |
p.0? |
- |
Promoter - exon 14 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11231199del |
- |
c.-187-?_2140+?del |
- |
LDLR_000009 |
predicted no protein; Deletion of exons 1-14
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Van der Graaf 2011 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_15i |
c.(?_-187)_(2311+1_2312-1)del |
r.(?) |
p.0? |
- |
Promoter - exon 15 |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11234021del |
- |
c.-187-?_2311+?del |
- |
LDLR_001272 |
predicted no protein; >36kb htz deletion of exons 1-15
Variant Error [EMISMATCH/EUNCERTAIN]: This transcript variant has an error. Please fix this entry and then remove this message. |
PubMed: Bertolini 2013 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_18_ |
c.(?_-187)_(*2584_?)del |
r.(?) |
p.0? |
- |
whole gene |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11244576del |
g.11089362_11133900del |
c.-187-?_*2584del |
- |
LDLR_000010 |
predicted no protein; deletion of whole gene; found in 1 proband, segregates with FH in 2 affected relatives and not in 2 unaffected relatives |
PubMed: Marduel 2010 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/+ |
_1_18_ |
c.(?_-187)_(*2584_?)del |
r.(?) |
p.0? |
- |
whole gene |
- |
- |
- |
- |
- |
ACGS |
pathogenic |
g.11200038_11244577del |
g.11089362_11133901del |
c.-187-?_*2584del |
- |
LDLR_000010 |
predicted no protein; deletion of whole gene |
PubMed: Usifo 2012 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-185_-183del |
r.(=) |
p.(=) |
- |
SREBP1 binding site |
- |
- |
- |
- |
5-15% LDLR activity when Htz with FH Pedi-1 (c.172delG, p.(Glu58Serfs*148)). 10% of wt luciferase activity |
ACGS |
likely pathogenic |
g.11200040_11200042del |
g.11089364_11089366del |
c.-185_-183delCTT, FH Pedi-2 |
- |
LDLR_000103 |
predicted reduced transcription; Hobb's numbering: -92_-90del; Variant reduces activity in luciferase assay without presence of FH Pedi-1 (c.172delG, p.(Glu58Serfs*148)); DNase I footprinting indicated that this variant abolished Sp1 binding to SREBP repeat 1 in the LDLR promoter |
PubMed: Peeters 1998 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-156C>T |
r.(=) |
p.(=) |
- |
SREBP2 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
Not tested |
ACGS |
likely pathogenic |
g.11200069C>T |
g.11089393C>T |
- |
- |
LDLR_001112 |
Hobbs' numbering -63C>T. Hmz, first report of Hmz variant in promotor. Co-segragated with FH in 1 affected sibling, not present in 1 unaffected sibling, 5 affected siblings not tested |
PubMed: Dedoussis 2004 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-155_-154delinsTTCTGCAAACTCCT |
r.(=) |
p.(=) |
- |
SREBP2 binding site |
- |
- |
- |
- |
11% of wt trascriptional activity (luciferase assay) |
ACGS |
likely pathogenic |
g.11200070_11200071delinsTTCTGCAAACTCCT |
g.11089394_11089395delinsTTCTGCAAACTCCT |
- |
- |
LDLR_001267 |
predicted reduced transcription; Nomenclature corrected from article (c; 155_-150delACCCCinsTTCTGCAAACTCCTCCC) |
PubMed: De Castro-Oros 2011 |
- |
- |
Germline |
- |
0.06 in this study |
- |
0 |
- |
Sarah Leigh |
?/? |
1 |
c.-153C>T |
r.(=) |
p.(=) |
- |
SREBP2 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
Not tested |
ACGS |
VUS |
g.11200072C>T |
g.11089396C>T |
- |
- |
LDLR_001116 |
Hobb's numbering -60C>T. Authors assumed this variant has a causal effect on the basis of its position in the promoter sequence, no evidence provided in this study. |
PubMed: Francova 2004 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-152C>T |
r.(=) |
p.(=) |
- |
SREBP2 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
40% of wt transcription using luciferase assay |
ACGS |
likely pathogenic |
g.11200073C>T |
g.11089397C>T |
- |
- |
LDLR_001266 |
predicted reduced transcription; Hobb's numbering: -59C>T. |
PubMed: Scholtz 1999 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-152C>T |
r.(=) |
p.(=) |
- |
SREBP2 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
40% of wt transcription using luciferase assay |
ACGS |
likely pathogenic |
g.11200073C>T |
g.11089397C>T |
- |
- |
LDLR_001266 |
predicted reduced transcription; Hobb's numbering: -59C>T. |
PubMed: Khoo 2000 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-152C>T |
r.(=) |
p.(=) |
- |
SREBP2 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
40% of wt transcription using luciferase assay |
ACGS |
likely pathogenic |
g.11200073C>T |
g.11089397C>T |
- |
- |
LDLR_001266 |
predicted reduced transcription; Hobb's numbering: -59C>T. |
PubMed: Brusgaard 2006 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/. |
- |
c.-152C>T |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
pathogenic |
g.11200073C>T |
g.11089397C>T |
LDLR(NM_000527.4):c.-152C>T |
- |
LDLR_001266 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
0 |
- |
VKGL-NL_AMC |
+?/. |
- |
c.-150A>G |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
likely pathogenic |
g.11200075A>G |
g.11089399A>G |
LDLR(NM_000527.4):c.-150A>G |
- |
LDLR_002040 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
VKGL-NL_AMC |
?/? |
1 |
c.-149C>A |
r.(=) |
p.(=) |
- |
SREBP2 binding site |
- |
- |
- |
- |
not tested |
ACGS |
VUS |
g.11200076C>A |
g.11089400C>A |
- |
- |
LDLR_001264 |
Hobb's numbering: -56C>A. |
PubMed: Tichy 2012 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
?/? |
1 |
c.-146C>A |
r.(=) |
p.(=) |
- |
SREBP2 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
Not tested |
ACGS |
VUS |
g.11200079C>A |
g.11089403C>A |
- |
- |
LDLR_001263 |
Hobb's numbering -53C>A |
PubMed: Day 1997 |
- |
- |
Germline |
- |
not in ExAC, June 2015 |
- |
0 |
- |
Sarah Leigh |
?/. |
- |
c.-143A>C |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
VUS |
g.11200082A>C |
g.11089406A>C |
LDLR(NM_000527.4):c.-143A>C |
- |
LDLR_002041 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
VKGL-NL_AMC |
+/. |
- |
c.-142C>G |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
pathogenic |
g.11200083C>G |
g.11089407C>G |
LDLR(NM_000527.4):c.-142C>G |
- |
LDLR_001923 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
0 |
- |
VKGL-NL_AMC |
?/? |
1 |
c.-142C>T |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
20% of wt transcription using luciferase assay & blocks ability to bind Sp1 (gel retardation assays). |
ACGS |
VUS |
g.11200083C>T |
g.11089407C>T |
- |
- |
LDLR_000857 |
predicted reduced transcription; Hobb's numbering -49; Reduced expression in luciferase reporter assay & blocks ability to bind Sp1 (gel retardation assays); No other variants found in proband, but some relatives with c.-142C>T do not have FH. |
PubMed: Mozas 2002 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
?/? |
1 |
c.-142C>T |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
20% of wt transcription using luciferase assay & blocks ability to bind Sp1 (gel retardation assays). |
ACGS |
VUS |
g.11200083C>T |
g.11089407C>T |
- |
- |
LDLR_000857 |
predicted reduced transcription; Hobb's numbering -49; Reduced expression in luciferase reporter assay & blocks ability to bind Sp1 (gel retardation assays); {PMID11792717:Mozas et al 2002 J Lipid Res 43 13} |
PubMed: Leren 2004 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-140C>G |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
7% transcriptional activity (luciferase assay). 25% reduction nuclear protein binding (EMSA assay){PMID21538688: De Castro-Oros 2011} |
ACGS |
likely pathogenic |
g.11200085C>G |
g.11089409C>G |
- |
- |
LDLR_000322 |
prediction reduced transcription |
PubMed: Alonso 2009 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-140C>G |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
7% of wt trascriptional activity (luciferase assay). 25% reduction of nuclear protein binding (EMSA assay) |
ACGS |
likely pathogenic |
g.11200085C>G |
g.11089409C>G |
- |
- |
LDLR_000322 |
prediction reduced transcription |
PubMed: De Castro-Oros 2011 |
- |
- |
Germline |
- |
0.3 in this study |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-140C>T |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
6% of wt trascriptional activity (luciferase assay). 25% reduction of nuclear protein binding in (EMSA assay) |
ACGS |
likely pathogenic |
g.11200085C>T |
g.11089409C>T |
- |
- |
LDLR_000323 |
predicted reduced transcription; Proband also carries c.858C>A, p.(Ser286Arg)(probably pathogenic) |
PubMed: De Castro-Oros 2011 |
- |
- |
Germline |
- |
0.06 in this study |
- |
0 |
- |
Sarah Leigh |
?/? |
1 |
c.-139C>A |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
Not tested |
ACGS |
VUS |
g.11200086C>A |
g.11089410C>A |
- |
- |
LDLR_001025 |
- |
PubMed: Fouchier 2005 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-139C>G |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
26% of wt using luciferase assay |
ACGS |
likely pathogenic |
g.11200086C>G |
g.11089410C>G |
- |
- |
LDLR_001190 |
predicted reduced transcription; Proband compound Htz with c.762_763inv, p.(Q254_C255delinsHG), inherited from mother & c.-22delC from father; Not found in 50 normals; Creates new initiation site, which could result in an novel peptide of 35aa. |
PubMed: Smith 2007 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/. |
- |
c.-139C>G |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
pathogenic |
g.11200086C>G |
g.11089410C>G |
LDLR(NM_000527.4):c.-139C>G |
- |
LDLR_001190 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
VKGL-NL_AMC |
+?/+? |
1 |
c.-138del |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
12/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
24% LDLR activity in Htz lymphocytes. Reduced level of expression |
ACGS |
likely pathogenic |
g.11200087del |
g.11089411del |
c.-138delT, FH Pyrgos |
- |
LDLR_000959 |
predicted reduced levels of transcription; Hobbs' numbering: -45delT. |
PubMed: Dedoussis 2003 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/. |
- |
c.-138del |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
pathogenic |
g.11200087del |
g.11089411del |
LDLR(NM_000527.4):c.-138delT |
- |
LDLR_000959 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
0 |
- |
VKGL-NL_AMC |
+?/+? |
1 |
c.-138T>C |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
12/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
Luciferase assay 43% of normal in the presence & 25% in the absence of sterols in the medium. |
ACGS |
likely pathogenic |
g.11200087T>C |
g.11089411T>C |
- |
- |
LDLR_000438 |
predicted reduced transcription; Hobbs' numbering: -45T>C |
PubMed: Sun 1995 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
?/? |
1 |
c.-137C>T |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
5-15% LDLR activity when Htz with c.1222G>A, p.(Glu408Lys), FH Algeria-1, FH Osaka |
ACGS |
VUS |
g.11200088C>T |
g.11089412C>T |
FH Albuquerque |
- |
LDLR_001262 |
Hobb's numbering: -44C>T. Found as compound Htz with c.1222G>A, p.(Glu408Lys) (FH-Algeria-1)(likely pathogenic). |
PubMed: Dedoussis 2003 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
?/? |
1 |
c.-137C>T |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
Not tested |
ACGS |
VUS |
g.11200088C>T |
g.11089412C>T |
FH Albuquerque |
- |
LDLR_001262 |
Hobb's numbering: -44C>T. Found as compound Htz with c.2054C>T, p.(Pro685Leu)(likely pathogenic). |
PubMed: Mak 1998 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/. |
- |
c.-137C>T |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
pathogenic |
g.11200088C>T |
g.11089412C>T |
LDLR(NM_000527.4):c.-137C>T |
- |
LDLR_001262 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
VKGL-NL_AMC |
+?/+? |
1 |
c.-136C>G |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
22% of wt trascriptional activity (luciferase assay). 30% reduction of nuclear protein binding in (EMSA assay) |
ACGS |
likely pathogenic |
g.11200089C>G |
g.11089413C>G |
Hobb’s -43C>T |
- |
LDLR_001260 |
prediction reduced transcription |
PubMed: De Castro-Oros 2011 |
- |
- |
Germline |
- |
0.06 in this study |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-136C>T |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
50% reduction of binding, internalization & degradation of labeled LDL in Htz fibroblasts compared with wt. Reduced mRNA levels; SP1 binding inhibited |
ACGS |
likely pathogenic |
g.11200089C>T |
g.11089413C>T |
Hobb’s -43C>T |
- |
LDLR_001261 |
predicted reduced transcription; co-segregated with the FH phenotype in six available family members; Abolished binding of Spi transcription factor to this site. |
PubMed: Koivisto 1994 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-136C>T |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
- |
ACGS |
likely pathogenic |
g.11200089C>T |
g.11089413C>T |
Hobb’s -43C>T |
- |
LDLR_001261 |
prediction reduced transcription |
PubMed: Kim 2004 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-136C>T |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
- |
ACGS |
likely pathogenic |
g.11200089C>T |
g.11089413C>T |
Hobb’s -43C>T |
- |
LDLR_001261 |
prediction reduced transcription |
PubMed: Leren 2004 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-136C>T |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
- |
ACGS |
likely pathogenic |
g.11200089C>T |
g.11089413C>T |
Hobb’s -43C>T |
- |
LDLR_001261 |
prediction reduced transcription |
PubMed: Fouchier 2005 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-136C>T |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
Transcription level of variant reduced to <5% of wt |
ACGS |
likely pathogenic |
g.11200089C>T |
g.11089413C>T |
Hobb’s -43C>T |
- |
LDLR_001261 |
prediction reduced transcription |
PubMed: Jensen 1996 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/. |
- |
c.-136C>T |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
pathogenic |
g.11200089C>T |
g.11089413C>T |
LDLR(NM_000527.4):c.-136C>T |
- |
LDLR_001261 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
VKGL-NL_AMC |
?/. |
_1 |
c.-135C>A |
r.(=) |
p.(?) |
Disease causing |
- |
- |
- |
- |
- |
- |
ACMG |
VUS |
g.11200090C>A |
g.11089414C>A |
g.5034C>A |
- |
LDLR_001906 |
- |
Journal: Banares 2017 |
- |
- |
Germline |
- |
1/33 cases |
- |
0 |
- |
Virginia Bañares |
+?/+? |
1 |
c.-135C>G |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
5-15% LDLR activity in Hmz. 11% trascriptional activity (luciferase assay){PMID21538688: De Castro-Oros 2011} |
ACGS |
likely pathogenic |
g.11200090C>G |
g.11089414C>G |
Hobb’s -42C>T; FH Columbia-2 |
- |
LDLR_000003 |
prediction reduced transcription |
PubMed: Hobbs 1992 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-135C>G |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
11% of wt trascriptional activity (luciferase assay){PMID21538688: De Castro-Oros et al, Hum Mutat. 2011 Aug;32(8):868-72} |
ACGS |
likely pathogenic |
g.11200090C>G |
g.11089414C>G |
Hobb’s -42C>T; FH Columbia-2 |
- |
LDLR_000003 |
prediction reduced transcription |
PubMed: Mozas 2004 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+ |
1 |
c.-135C>G |
r.(=) |
p.(0) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
11% of wt trascriptional activity (luciferase assay){PMID21538688: De Castro-Oros et al, Hum Mutat. 2011 Aug;32(8):868-72} |
ACGS |
likely pathogenic |
g.11200090C>G |
g.11089414C>G |
Hobb’s -42C>T; FH Columbia-2 |
- |
LDLR_000003 |
predicted reduced transcription; On the same allele as c.1185G>C, p.(Val395Val) |
PubMed: Bourbon 2009 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/? |
1 |
c.-135C>G |
r.(=) |
p.(=) |
- |
SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
11% of wt trascriptional activity (luciferase assay){PMID21538688: De Castro-Oros et al, Hum Mutat. 2011 Aug;32(8):868-72} |
ACGS |
likely pathogenic |
g.11200090C>G |
g.11089414C>G |
Hobb’s -42C>T; FH Columbia-2 |
- |
LDLR_000003 |
prediction reduced transcription |
PubMed: Medeiros 2010 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+/. |
- |
c.-135C>G |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
pathogenic |
g.11200090C>G |
g.11089414C>G |
LDLR(NM_000527.4):c.-135C>G |
- |
LDLR_000003 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
0 |
- |
VKGL-NL_AMC |
?/. |
1 |
c.-134C>A |
r.(=) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
VUS |
g.11200091C>A |
g.11089415C>A |
- |
- |
LDLR_002179 |
- |
Journal: Gomez 2017 |
- |
- |
Germline/De novo (untested) |
- |
- |
- |
0 |
- |
Andrea Gomez |
?/. |
- |
c.-122C>T |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
VUS |
g.11200103C>T |
g.11089427C>T |
LDLR(NM_000527.4):c.-122C>T |
- |
LDLR_002042 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
VKGL-NL_AMC |
+?/+? |
1 |
c.-121T>C |
r.(=) |
p.(=) |
- |
TATA box/SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
72% of WT promoter activity (luciferase assay) {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
ACGS |
likely pathogenic |
g.11200104T>C |
g.11089428T>C |
- |
- |
LDLR_000002 |
predicted reduced transcription; 72% of WT promoter activity {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
PubMed: Taylor 2010 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-121T>C |
r.(=) |
p.(=) |
- |
TATA box/SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
72% of WT promoter activity (luciferase assay) {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
ACGS |
likely pathogenic |
g.11200104T>C |
g.11089428T>C |
- |
- |
LDLR_000002 |
predicted reduced transcription; 72% of WT promoter activity {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
PubMed: Hooper 2012 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-120C>T |
r.(=) |
p.(=) |
- |
TATA box/SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
3% of WT promoter activity (luciferase assay) |
ACGS |
likely pathogenic |
g.11200105C>T |
g.11089429C>T |
Hobb’s -27C>T |
- |
LDLR_001115 |
predicted reduced transcription; co-segregated with FH in 3 siblings, father not available on not present in mother; Not present in 50 normal controls |
PubMed: Francova 2004 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-120C>T |
r.(=) |
p.(=) |
- |
TATA box/SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
3% of WT promoter activity (luciferase assay) |
ACGS |
likely pathogenic |
g.11200105C>T |
g.11089429C>T |
Hobb’s -27C>T |
- |
LDLR_001115 |
predicted reduced transcription; co-segregated with FH in 3 siblings, father not available on not present in mother; Not present in 50 normal controls |
PubMed: Francova 2004 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-120C>T |
r.(=) |
p.(=) |
- |
TATA box/SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
3% of WT promoter activity (luciferase assay) |
ACGS |
likely pathogenic |
g.11200105C>T |
g.11089429C>T |
Hobb’s -27C>T |
- |
LDLR_001115 |
predicted reduced transcription; co-segregated with FH in 3 siblings, father not available on not present in mother; Not present in 50 normal controls |
PubMed: Francova 2004 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/+? |
1 |
c.-120C>T |
r.(=) |
p.(=) |
- |
TATA box/SP1 binding site |
- |
- |
13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
3% of WT promoter activity (luciferase assay) |
ACGS |
likely pathogenic |
g.11200105C>T |
g.11089429C>T |
Hobb’s -27C>T |
- |
LDLR_001115 |
prediction reduced transcription |
PubMed: Alonso 2009 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
+?/. |
- |
c.-120C>T |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
likely pathogenic |
g.11200105C>T |
g.11089429C>T |
LDLR(NM_000527.4):c.-120C>T |
- |
LDLR_001115 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
0 |
- |
VKGL-NL_AMC |
?/+? |
1 |
c.-101T>C |
r.(=) |
p.(=) |
- |
TATA box |
- |
- |
12/12 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
64% of WT promoter activity (luciferase assay) {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
ACGS |
VUS |
g.11200124T>C |
g.11089448T>C |
- |
- |
LDLR_000001 |
predicted reduced transcription; 64% of WT promoter activity (luciferase assay) {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
PubMed: Usifo 2012 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
?/. |
- |
c.-98C>T |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
VUS |
g.11200127C>T |
g.11089451C>T |
LDLR(NM_000527.4):c.-98C>T |
- |
LDLR_001925 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
0 |
- |
VKGL-NL_Groningen |
-?/-? |
1 |
c.-88G>A |
r.(=) |
p.(=) |
- |
5'UTR |
- |
- |
12/12 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
Normal levels of transcription (luciferase assay in HEPG2 cells) |
ACGS |
likely benign |
g.11200137G>A |
g.11089461G>A |
- |
- |
LDLR_001270 |
prediction no effect on transcription |
PubMed: De Castro-Oros 2011 |
- |
- |
Germline |
- |
0.06 in this study |
- |
0 |
- |
Sarah Leigh |
?/? |
1 |
c.-68A>C |
r.(=) |
p.(=) |
- |
5'UTR |
- |
- |
5/11 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
not tested |
ACGS |
VUS |
g.11200157A>C |
g.11089481A>C |
- |
- |
LDLR_001121 |
- |
PubMed: Laurie 2004 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
?/. |
- |
c.-48A>G |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
VUS |
g.11200177A>G |
g.11089501A>G |
LDLR(NM_000527.4):c.-48A>G |
- |
LDLR_002216 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
VKGL-NL_AMC |
-?/. |
- |
c.-47G>T |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
likely benign |
g.11200178G>T |
- |
LDLR(NM_000527.4):c.-47G>T |
- |
LDLR_002221 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
VKGL-NL_AMC |
-?/-? |
1 |
c.-36T>G |
r.(=) |
p.(=) |
- |
5'UTR |
- |
- |
6/12 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
Normal levels of transcription (luciferase assay in HEPG2 cells) |
ACGS |
likely benign |
g.11200189T>G |
g.11089513T>G |
- |
- |
LDLR_001269 |
prediction no effect on transcription |
PubMed: De Castro-Oros 2011 |
- |
- |
Germline |
- |
0.06 in this study |
- |
0 |
- |
Sarah Leigh |
?/? |
1 |
c.-23A>C |
r.(=) |
p.(=) |
- |
5'UTR |
- |
- |
7/12 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} |
- |
not tested |
ACGS |
VUS |
g.11200202A>C |
g.11089526A>C |
- |
- |
LDLR_000815 |
- |
PubMed: Mozas 2004 |
- |
- |
Germline |
- |
- |
- |
0 |
- |
Sarah Leigh |
?/. |
- |
c.-22C>T |
r.(?) |
p.(=) |
- |
- |
- |
- |
- |
- |
- |
- |
VUS |
g.11200203C>T |
g.11089527C>T |
LDLR(NM_000527.4):c.-22C>T |
- |
LDLR_002181 |
VKGL data sharing initiative Nederland |
- |
- |
- |
CLASSIFICATION record |
- |
- |
- |
- |
- |
VKGL-NL_AMC |