Full data view for gene LDLR

Information The variants shown are described using the NM_000527.4 transcript reference sequence.

4178 entries on 42 pages. Showing entries 1 - 100.
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Enzyme activity     

Predict-BioInf     

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Clinical classification     

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+/+ _1_2i c.-1823_190+566del r.(?) p.0? Promoter - exon 2 - - Parent #1 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 - - - DNA SEQ - - FH - PubMed: Goldmann 2010 - - - Czech Republic Unknown - - - - 1 Sarah Leigh
+/. _1_1i c.-1818_67+1091delinsTTC r.0? p.0? - - - Paternal (confirmed) - 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 - - - - DNA SEQ-NG - - FH Fam1PatI1 PubMed: Wong 2019, Journal: Wong 2019 3-generation family F - United States white - - - - 1 Karen HY Wong
?/. - c.-342C>A r.(?) p.(=) - - - Unknown - VUS g.11199883C>A - LDLR(NM_000527.5):c.-342C>A - LDLR_002379 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.-309C>A r.(?) p.(=) - - - Unknown - likely benign g.11199916C>A - LDLR(NM_000527.5):c.-309C>A - LDLR_002380 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.-283G>C r.(?) p.(=) - - - Unknown - VUS g.11199942G>C - LDLR(NM_000527.5):c.-283G>C - LDLR_002298 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/-? _1 c.-268G>T r.(=) p.? FP2 cis acting regulatory element Transient transfection in HepG2 cells demonstrated conservation: 7/8 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Scholtz 1999 - - - South Africa Indigenous ZA - - - - 1 Sarah Leigh
-?/-? _1 c.-268G>T r.(=) p.? FP2 cis acting regulatory element limited effect on LDLR activity conservation: 7/8 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 ACGS likely benign g.11199957G>T g.11089281G>T - - LDLR_000374 - PubMed: Whittall 2002 - - Germline - - - - - DNA SEQ - - FH - PubMed: Whittall 2002 - - - United Kingdom (Great Britain) Indigenous African - - - - 1 Sarah Leigh
-?/. - c.-268G>T r.(?) p.(=) - - - Unknown - likely benign g.11199957G>T g.11089281G>T LDLR(NM_000527.5):c.-268G>T - LDLR_000374 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/? _1 c.-221_-220insA r.(=) p.? FP1 cis acting regulatory element - - Parent #1 ACGS VUS g.11200005dup g.11089329dup - - LDLR_000950 - PubMed: Bodamer 2002 - - Germline - - - - - DNA SEQ - - FH - PubMed: Bodamer 2002 - - - United States US - - - - 1 Sarah Leigh
-?/-? _1 c.-217C>T r.(=) p.? FP1 cis acting regulatory element 160% luciferase activity compared to wt {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Scholtz 1999 - - - South Africa Mixed - - - - 1 Sarah Leigh
-?/? _1 c.-217C>T r.(=) p.? FP1 cis acting regulatory element 160% luciferase activity compared to wt {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Both (homozygous) 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 - - - - - DNA PCR, SEQ - - FH - PubMed: Snozek 2009 - - - United States African American - - - - 1 Sarah Leigh
-?/. - c.-217C>T r.(?) p.(=) - - - Unknown - likely benign g.11200008C>T - LDLR(NM_000527.5):c.-217C>T - LDLR_000015 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/? _1 c.-215A>G r.(=) p.? FP1 cis acting regulatory element 100% luciferase activity compared to wt {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} conservation: 11/12 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 ACGS likely benign g.11200010A>G g.11089334A>G - - LDLR_000006 prediction no effect on transcription PubMed: Usifo 2012 - - Germline - - - - - DNA SEQ - - FH - PubMed: Usifo 2012 - - - United Kingdom (Great Britain) Unknown - - - - 1 Sarah Leigh
-?/-? _1 c.-208A>T r.(=) p.? SREBP1/FP1 100% of wt trascriptional activity (luciferase assay). conservation: 12/12 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - DNA PCR, SEQ peripheral blood - FH - PubMed: De Castro-Oros 2011 Proband from FH family, with CVD. No variants identified from Lipochip v3–v8 (Progenika Biopharma, Derio, Spain). LDL-C = >270 mg/dl - - Spain Spanish - - - - 1 Sarah Leigh
?/? _1 c.-206C>T r.(=) p.? SREBP1/FP1 not tested conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 ACGS VUS g.11200019C>T g.11089343C>T - - LDLR_001010 - PubMed: Lind 2002 - - Germline - - - - - DNA SEQ - - FH - PubMed: Lind 2002 - - - Sweden SE - - - - 1 Sarah Leigh
?/? _1 c.-193_-186delinsTG r.(=) p.? SREBP1 binding site not tested - Parent #1 ACGS VUS g.11200032_11200039delinsTG g.11089356_11089363delinsTG - - LDLR_001024 - PubMed: Fouchier 2005 - - Germline - - - - - DNA SEQ - - FH - PubMed: Fouchier 2005 - - - Netherlands NL - - - - 1 Sarah Leigh
?/? _1 c.-188C>T r.(=) p.? SREBP1 binding site not tested conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 ACGS VUS g.11200037C>T g.11089361C>T - - LDLR_001023 - PubMed: Fouchier 2005 - - Germline - - - - - DNA SEQ - - FH - PubMed: Fouchier 2005 - - - Netherlands NL - - - - 1 Sarah Leigh
+?/. - c.-187C>T r.(?) p.(=) - - - Unknown - likely pathogenic g.11200038C>T g.11089362C>T LDLR(NM_000527.5):c.-187C>T - LDLR_002180 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/. - c.-187_-185del r.(?) p.(=) - - - Unknown - likely pathogenic g.11200038_11200040del - LDLR(NM_000527.5):c.-187_-185delCTC - LDLR_002381 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/+ _1_1i c.(?_-187)_(67+1_68-1)del r.(?) p.0? promotor & exon 1 - - Parent #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 - - - - - DNA SEQ - - FH - PubMed: Fouchier 2005 - - - Netherlands Unknown - - - - 1 Sarah Leigh
+/+ _1_1i c.(?_-187)_(67+1_68-1)del r.(?) p.0? Promotor - exon 1 - - Parent #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 - - - - - DNA SEQ - - FH - PubMed: Chaves 2001 - - - Spain ES - - - - 1 Sarah Leigh
+/+ _1_1i c.(?_-187)_(67+1_68-1)del r.(?) p.0? Promotor - exon 1 - - Parent #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 - - - - - DNA SEQ - - FH - PubMed: Fouchier 2005 - - - Netherlands NL - - - - 1 Sarah Leigh
+/+ _1_1i c.(?_-187)_(67+1_68-1)del r.(?) p.0? Promotor - exon 1 - - Parent #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 - - - DNA SEQ - - FH - PubMed: Tichy 2012 - - - Czech Republic Unknown - - - - 1 Sarah Leigh
+/+ _1_1i c.(?_-187)_(67+1_68-1)del r.(?) p.0? Promotor - exon 1 - - Parent #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 - - - - - DNA SEQ - - FH - PubMed: Koeijvoets 2005 - - - Netherlands NL - - - - 1 Sarah Leigh
+/+ _1_1i c.(?_-187)_(67+1_68-1)del r.(?) p.0? Promoter - exon 1 - - Parent #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 - - - - - DNA SEQ - - FH - PubMed: Nissen 2006 - - - Denmark DK - - - - 1 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 - Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Hobbs 1988 - - - United States US - - - - 1 Sarah Leigh
+/+ _1_1i c.(?_-187)_(67+1_68-1)del r.(?) p.0? Promotor - exon 1 <2% LDLR activity in Hmz - Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Hobbs 1987 - - - Canada French Canadian - - - - 1 Sarah Leigh
+/+ _1_1i c.(?_-187)_(67+1_68-1)del r.(?) p.0? Promotor - exon 1 - - Parent #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 - - - DNA MLPA - - FH - PubMed: Marduel 2010 - - - France Unknown - - - - 1 Sarah Leigh
+/+ _1_1i c.(?_-187)_(67+1_68-1)del r.(?) p.0? Promotor - exon 1 - - Parent #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 - - - DNA MLPA peripheral blood - FH - PubMed: Sharifi 2016 - - - Poland white - - - - 1 Sarah Leigh
+?/+? _1_1i c.(?_-187)_(67+1_68-1)dup r.(?) p.0? Promotor - exon 1 - - Parent #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 - - - DNA MLPA peripheral blood - FH - PubMed: Sharifi 2016 - - - Poland white - - - - 1 Sarah Leigh
+/+ _1_2i c.(?_-187)_(190+1_191-1)del r.(?) p.0? Promotor - exon 2 - - Parent #1 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 - - - DNA SEQ - - FH - PubMed: Chmara 2010 - - - Poland Unknown - - - - 1 Sarah Leigh
+/+ _1_2i c.(?_-187)_(190+1_191-1)del r.(?) p.0? Promotor - exon 2 - - Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Chaves 2001 - - - Spain ES - - - - 1 Sarah Leigh
+/+ _1_2i c.(?_-187)_(190+1_191-1)del r.(?) p.0? Promotor - exon 2 - - Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Koeijvoets 2005 - - - Netherlands NL - - - - 1 Sarah Leigh
+/+ _1_2i c.(?_-187)_(190+1_191-1)del r.(?) p.0? Promotor - exon 2 45% LDLR activity in Htz fibroblasts - Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Garuti 1996 - - - Italy IT - - - - 1 Sarah Leigh
+/+ _1_2i c.[(?_-187)_(190+1_191-1)del;(1060+1_1061-1)_(1845+1_1846-1)del] r.(?) p.0? Promoter - exon 2 & exons 8-12 - - Parent #1 ACGS pathogenic g.[11200038_11211021del;11222190_11227674del] - c.[-187-?_190+?del;1061-?_1845+?del] - LDLR_000000 predicted no protein; Deletion of promoter, exons 1 & 2 allelic with deletion of exons 8-12; Found in 8 relatives of the proband PubMed: Bourbon 2008 - - Germline - - - - - DNA SEQ - - FH - PubMed: Bourbon 2008 - - - Portugal Unknown - - - - 1 Sarah Leigh
+/+ _1_2i c.[(?_-187)_(190+1_191-1)del;(1060+1_1061-1)_(1845+1_1846-1)del] r.(?) p.0? Promoter - exon 2 & exons 8-12 - - Parent #1 ACGS pathogenic g.[11200038_11211021del;11222190_11227674del] - c.[-187-?_190+?del;1061-?_1845+?del] - LDLR_000000 predicted no protein; Deletion of exons 1 & 2 and exons 8-12; Found in 2 probands but may be different deletions in each. PubMed: Marduel 2010 - - Germline - - - - - DNA MLPA - - FH - PubMed: Marduel 2010 - - - France Unknown - - - - 1 Sarah Leigh
+/+ _1_6i c.(?_-187)_(940+1_941-1)del r.(?) p.0? Promoter - exon 6 - - Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Sun 1992 - - - United Kingdom (Great Britain) GB - - - - 1 Sarah Leigh
+/+ _1_6i c.(?_-187)_(940+1_941-1)del r.(?) p.0? Promoter - exon 6 - - Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Bertolini 2000 - - - Italy IT - - - - 1 Sarah Leigh
+/+ _1_6i c.(?_-187)_(940+1_941-1)del r.(?) p.0? Promoter - exon 6 40-50% LDLR activity in Htz - Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Lelli 1991 - - - Italy IT - - - - 1 Sarah Leigh
+/+ _1_7i c.(?_-187)_(1060+1_1061-1)del r.(?) p.0? Promoter - exon 7 - - Parent #1 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 - - - - - DNA MLPA - - FH - PubMed: Marduel 2010 - - - France Unknown - - - - 1 Sarah Leigh
+/+ _1_8i c.(?_-187)_(1186+1_1187-1)del r.(?) p.0? Promoter - exon 8 - - Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Fouchier 2005 - - - Netherlands NL - - - - 1 Sarah Leigh
+/+ _1_12i c.(?_-187)_(1845+1_1846-1)del r.(?) p.0? Promoter - exon 12 - - Parent #1 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 - - - - - DNA SEQ peripheral blood - FH - PubMed: Shin 2015 - - - Korea, South (Republic) KR - - - - 1 Sarah Leigh
+/+ _1_14i c.(?_-187)_(2140+1_2141-1)del r.(?) p.0? Promoter - exon 14 - - Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Van der Graaf 2011 - - - Netherlands Unknown - - - - 1 Sarah Leigh
+/+ _1_15i c.(?_-187)_(2311+1_2312-1)del r.(?) p.0? Promoter - exon 15 - - Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Bertolini 2013 - - - Italy IT - - - - 1 Sarah Leigh
+/+ _1_18_ c.(?_-187)_(*2584_?)del r.(?) p.0? whole gene - - Parent #1 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 - - - - - DNA MLPA - - FH - PubMed: Marduel 2010 - - - France Unknown - - - - 1 Sarah Leigh
+/+ _1_18_ c.(?_-187)_(*2584_?)del r.(?) p.0? whole gene - - Parent #1 ACGS pathogenic g.11200038_11244577del g.11089362_11133901del c.-187-?_*2584del - LDLR_000010 predicted no protein; deletion of whole gene PubMed: Usifo 2012 - - Germline - - - - - DNA SEQ - - FH - PubMed: Usifo 2012 - - - United Kingdom (Great Britain) Unknown - - - - 1 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 - Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Peeters 1998 - - - South Africa Pedi tribe - - - - 1 Sarah Leigh
+?/+? 1 c.-156C>T r.(=) p.(=) SREBP2 binding site Not tested conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Dedoussis 2004 - - - Germany DE - - - - 1 Sarah Leigh
+?/. - c.-156C>T r.(?) p.(=) - - - Unknown - likely pathogenic g.11200069C>T - LDLR(NM_000527.5):c.-156C>T - LDLR_001112 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/+? 1 c.-155_-154delinsTTCTGCAAACTCCT r.(=) p.(=) SREBP2 binding site 11% of wt trascriptional activity (luciferase assay) - Parent #1 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 - - - DNA PCR, SEQ peripheral blood - FH - PubMed: De Castro-Oros 2011 Proband from FH family, with TX and CVD. No variants identified from Lipochip v3–v8 (Progenika Biopharma, Derio, Spain). LDL-C = >330 mg/dl - - Spain Spanish - - - - 1 Sarah Leigh
?/? 1 c.-153C>T r.(=) p.(=) SREBP2 binding site Not tested conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Francova 2004 - - - Czech Republic CZ - - - - 1 Sarah Leigh
+?/+? 1 c.-152C>T r.(=) p.(=) SREBP2 binding site 40% of wt transcription using luciferase assay conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 ACGS likely pathogenic g.11200073C>T g.11089397C>T - - LDLR_001266 predicted reduced transcription; Hobb's numbering: -59C>T. PubMed: Scholtz 1999 - - Germline - - - - - DNA SEQ - - FH - PubMed: Scholtz 1999 - - - South Africa non-European - - - - 1 Sarah Leigh
+?/+? 1 c.-152C>T r.(=) p.(=) SREBP2 binding site 40% of wt transcription using luciferase assay conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 ACGS likely pathogenic g.11200073C>T g.11089397C>T - - LDLR_001266 predicted reduced transcription; Hobb's numbering: -59C>T. PubMed: Khoo 2000 - - Germline - - - - - DNA SEQ - - FH - PubMed: Khoo 2000 - - - China CN - - - - 1 Sarah Leigh
+?/+? 1 c.-152C>T r.(=) p.(=) SREBP2 binding site 40% of wt transcription using luciferase assay conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 ACGS likely pathogenic g.11200073C>T g.11089397C>T - - LDLR_001266 predicted reduced transcription; Hobb's numbering: -59C>T. PubMed: Brusgaard 2006 - - Germline - - - - - DNA SEQ - - FH - PubMed: Brusgaard 2006 - - - Denmark DK - - - - 1 Sarah Leigh
+/. - c.-152C>T r.(?) p.(=) - - - Unknown - pathogenic g.11200073C>T g.11089397C>T LDLR(NM_000527.5):c.-152C>T - LDLR_001266 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/. - c.-150A>G r.(?) p.(=) - - - Unknown - likely pathogenic g.11200075A>G g.11089399A>G LDLR(NM_000527.5):c.-150A>G - LDLR_002040 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/? 1 c.-149C>A r.(=) p.(=) SREBP2 binding site not tested - Parent #1 ACGS VUS g.11200076C>A g.11089400C>A - - LDLR_001264 Hobb's numbering: -56C>A. PubMed: Tichy 2012 - - Germline - - - - - DNA SEQ - - FH - PubMed: Tichy 2012 - - - Czech Republic Unknown - - - - 1 Sarah Leigh
?/? 1 c.-146C>A r.(=) p.(=) SREBP2 binding site Not tested conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 ACGS VUS g.11200079C>A g.11089403C>A - - LDLR_001263 Hobb's numbering -53C>A PubMed: Day 1997 - - Germline - not in ExAC, June 2015 - - - DNA SEQ - - FH - PubMed: Day 1997 - - - United Kingdom (Great Britain) GB - - - - 1 Sarah Leigh
?/. - c.-143A>C r.(?) p.(=) - - - Unknown - VUS g.11200082A>C g.11089406A>C LDLR(NM_000527.5):c.-143A>C - LDLR_002041 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/. - c.-142C>G r.(?) p.(=) - - - Unknown - pathogenic g.11200083C>G g.11089407C>G LDLR(NM_000527.5):c.-142C>G - LDLR_001923 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/? 1 c.-142C>T r.(=) p.(=) SP1 binding site 20% of wt transcription using luciferase assay & blocks ability to bind Sp1 (gel retardation assays). conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Mozas 2002 - - - Spain ES - - - - 1 Sarah Leigh
?/? 1 c.-142C>T r.(=) p.(=) SP1 binding site 20% of wt transcription using luciferase assay & blocks ability to bind Sp1 (gel retardation assays). conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ peripheral blood - FH - PubMed: Leren 2004 - - - Norway Unknown - - - - 1 Sarah Leigh
+?/+? 1 c.-140C>G r.(=) p.(=) SP1 binding site 7% transcriptional activity (luciferase assay). 25% reduction nuclear protein binding (EMSA assay){PMID21538688: De Castro-Oros 2011} conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 ACGS likely pathogenic g.11200085C>G g.11089409C>G - - LDLR_000322 prediction reduced transcription PubMed: Alonso 2009 - - Germline - - - - - DNA SEQ - - FH - PubMed: Alonso 2009 - - - Spain ES - - - - 1 Sarah Leigh
+?/+? 1 c.-140C>G r.(=) p.(=) SP1 binding site 7% of wt trascriptional activity (luciferase assay). 25% reduction of nuclear protein binding (EMSA assay) conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - DNA PCR, SEQ peripheral blood - FH - PubMed: De Castro-Oros 2011 Proband from FH family, with TX. No variants identified from Lipochip v3–v8 (Progenika Biopharma, Derio, Spain). LDL-C = 270 mg/dl - - Spain Spanish - - - - 1 Sarah Leigh
+?/+? 1 c.-140C>T r.(=) p.(=) SP1 binding site 6% of wt trascriptional activity (luciferase assay). 25% reduction of nuclear protein binding in (EMSA assay) conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - DNA PCR, SEQ peripheral blood - FH - PubMed: De Castro-Oros 2011 Proband from FH family, with CVD. No variants identified from Lipochip v3–v8 (Progenika Biopharma, Derio, Spain). LDL-C = 415 mg/dl - - Spain Spanish - - - - 1 Sarah Leigh
?/? 1 c.-139C>A r.(=) p.(=) SP1 binding site Not tested conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 ACGS VUS g.11200086C>A g.11089410C>A - - LDLR_001025 - PubMed: Fouchier 2005 - - Germline - - - - - DNA SEQ - - FH - PubMed: Fouchier 2005 - - - Netherlands NL - - - - 1 Sarah Leigh
+?/+? 1 c.-139C>G r.(=) p.(=) SP1 binding site 26% of wt using luciferase assay conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SSCA - - FH - PubMed: Smith 2007 - - - United Kingdom (Great Britain) TR - - - - 1 Sarah Leigh
+/. - c.-139C>G r.(?) p.(=) - - - Unknown - pathogenic g.11200086C>G g.11089410C>G LDLR(NM_000527.5):c.-139C>G - LDLR_001190 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/+? 1 c.-138del r.(=) p.(=) SP1 binding site 24% LDLR activity in Htz lymphocytes. Reduced level of expression conservation: 12/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Dedoussis 2003 - - - Greece GR - - - - 1 Sarah Leigh
+/. - c.-138del r.(?) p.(=) - - - Unknown - pathogenic g.11200087del g.11089411del LDLR(NM_000527.5):c.-138delT - LDLR_000959 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/+? 1 c.-138T>C r.(=) p.(=) SP1 binding site Luciferase assay 43% of normal in the presence & 25% in the absence of sterols in the medium. conservation: 12/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 ACGS likely pathogenic g.11200087T>C g.11089411T>C - - LDLR_000438 predicted reduced transcription; Hobbs' numbering: -45T>C PubMed: Sun 1995 - - Germline - - - - - DNA SEQ - - FH - PubMed: Sun 1995 - - - United Kingdom (Great Britain) Welsh - - - - 1 Sarah Leigh
?/? 1 c.-137C>T r.(=) p.(=) SP1 binding site 5-15% LDLR activity when Htz with c.1222G>A, p.(Glu408Lys), FH Algeria-1, FH Osaka conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Dedoussis 2003 - - - United States US - - - - 1 Sarah Leigh
?/? 1 c.-137C>T r.(=) p.(=) SP1 binding site Not tested conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Mak 1998 - - - China CN - - - - 1 Sarah Leigh
+/. - c.-137C>T r.(?) p.(=) - - - Unknown - pathogenic g.11200088C>T g.11089412C>T LDLR(NM_000527.5):c.-137C>T - LDLR_001262 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/+? 1 c.-136C>G r.(=) p.(=) SP1 binding site 22% of wt trascriptional activity (luciferase assay). 30% reduction of nuclear protein binding in (EMSA assay) conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - DNA PCR, SEQ peripheral blood - FH - PubMed: De Castro-Oros 2011 Proband from FH family, with CVD. No variants identified from Lipochip v3–v8 (Progenika Biopharma, Derio, Spain). LDL-C = >500 mg/dl - - Spain Spanish - - - - 1 Sarah Leigh
+?/+? 1 c.-136C>T r.(=) p.(=) SP1 binding site - conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 ACGS likely pathogenic g.11200089C>T g.11089413C>T Hobb’s -43C>T - LDLR_001261 prediction reduced transcription PubMed: Kim 2004 - - Germline - - - - - DNA SEQ - - FH - PubMed: Kim 2004 - - - Korea, South (Republic) KR - - - - 1 Sarah Leigh
+?/+? 1 c.-136C>T r.(=) p.(=) SP1 binding site - conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 ACGS likely pathogenic g.11200089C>T g.11089413C>T Hobb’s -43C>T - LDLR_001261 prediction reduced transcription PubMed: Leren 2004 - - Germline - - - - - DNA SEQ peripheral blood - FH - PubMed: Leren 2004 - - - Norway Unknown - - - - 1 Sarah Leigh
+?/+? 1 c.-136C>T r.(=) p.(=) SP1 binding site - conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 ACGS likely pathogenic g.11200089C>T g.11089413C>T Hobb’s -43C>T - LDLR_001261 prediction reduced transcription PubMed: Fouchier 2005 - - Germline - - - - - DNA SEQ - - FH - PubMed: Fouchier 2005 - - - Netherlands NL - - - - 1 Sarah Leigh
+?/+? 1 c.-136C>T r.(=) p.(=) SP1 binding site 50% reduction of binding, internalization & degradation of labeled LDL in Htz fibroblasts compared with wt. Reduced mRNA levels; SP1 binding inhibited conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Koivisto 1994 - - - Finland Finland - - - - 1 Sarah Leigh
+?/+? 1 c.-136C>T r.(=) p.(=) SP1 binding site Transcription level of variant reduced to <5% of wt conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 ACGS likely pathogenic g.11200089C>T g.11089413C>T Hobb’s -43C>T - LDLR_001261 prediction reduced transcription PubMed: Jensen 1996 - - Germline - - - - - DNA SEQ - - FH - PubMed: Jensen 1996 - - - Denmark DK - - - - 1 Sarah Leigh
+/. - c.-136C>T r.(?) p.(=) - - - Unknown - pathogenic g.11200089C>T g.11089413C>T LDLR(NM_000527.5):c.-136C>T - LDLR_001261 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. _1 c.-135C>A r.(=) p.(?) - - MutationTaster: Disease causing Unknown ACMG VUS g.11200090C>A g.11089414C>A g.5034C>A - LDLR_001906 - Journal: Banares 2017 - - Germline - 1/33 cases - - - DNA SEQ - - FH ? Journal: Banares 2017 - - - Argentina - - - - - 1 Virginia Bañares
+?/+? 1 c.-135C>G r.(=) p.(=) SP1 binding site 5-15% LDLR activity in Hmz. 11% trascriptional activity (luciferase assay){PMID21538688: De Castro-Oros 2011} conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Hobbs 1992 - - - Colombia CO - - - - 1 Sarah Leigh
+?/+? 1 c.-135C>G r.(=) p.(=) SP1 binding site 11% of wt trascriptional activity (luciferase assay){PMID21538688: De Castro-Oros et al, Hum Mutat. 2011 Aug;32(8):868-72} conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Mozas 2004 - - - Spain ES - - - - 1 Sarah Leigh
+?/+ 1 c.-135C>G r.(=) p.(0) SP1 binding site 11% of wt trascriptional activity (luciferase assay){PMID21538688: De Castro-Oros et al, Hum Mutat. 2011 Aug;32(8):868-72} conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Bourbon 2009 - - - Portugal Unknown - - - - 1 Sarah Leigh
+?/? 1 c.-135C>G r.(=) p.(=) SP1 binding site 11% of wt trascriptional activity (luciferase assay){PMID21538688: De Castro-Oros et al, Hum Mutat. 2011 Aug;32(8):868-72} conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA DHPLC, SEQ - - FH - PubMed: Medeiros 2010 - - - Portugal Unknown - - - - 1 Sarah Leigh
+/. - c.-135C>G r.(?) p.(=) - - - Unknown - pathogenic g.11200090C>G g.11089414C>G LDLR(NM_000527.5):c.-135C>G - LDLR_000003 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. 1 c.-134C>A r.(=) p.(=) - - - Unknown - VUS g.11200091C>A g.11089415C>A - - LDLR_002179 - Journal: Gomez 2017 - - Germline/De novo (untested) - - - - - DNA SEQ - - FH - Journal: Gomez 2017 - - - Argentina - - - - - 1 Andrea Gomez
?/. - c.-122C>T r.(?) p.(=) - - - Unknown - VUS g.11200103C>T g.11089427C>T LDLR(NM_000527.5):c.-122C>T - LDLR_002042 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/+? 1 c.-121T>C r.(=) p.(=) TATA box/SP1 binding site 72% of WT promoter activity (luciferase assay) {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Taylor 2010 - - - United Kingdom (Great Britain) Unknown - - - - 1 Sarah Leigh
+?/+? 1 c.-121T>C r.(=) p.(=) TATA box/SP1 binding site 72% of WT promoter activity (luciferase assay) {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA PCR, SEQ peripheral blood - FH - PubMed: Hooper 2012 - - - Australia Unknown - - - - 1 Sarah Leigh
+?/+? 1 c.-120C>T r.(=) p.(=) TATA box/SP1 binding site 3% of WT promoter activity (luciferase assay) conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Francova 2004 - - - Czech Republic CZ - - - - 1 Sarah Leigh
+?/+? 1 c.-120C>T r.(=) p.(=) TATA box/SP1 binding site 3% of WT promoter activity (luciferase assay) conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Francova 2004 - - - Czech Republic CZ - - - - 1 Sarah Leigh
+?/+? 1 c.-120C>T r.(=) p.(=) TATA box/SP1 binding site 3% of WT promoter activity (luciferase assay) conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Francova 2004 - - - Czech Republic CZ - - - - 1 Sarah Leigh
+?/+? 1 c.-120C>T r.(=) p.(=) TATA box/SP1 binding site 3% of WT promoter activity (luciferase assay) conservation: 13/13 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 ACGS likely pathogenic g.11200105C>T g.11089429C>T Hobb’s -27C>T - LDLR_001115 prediction reduced transcription PubMed: Alonso 2009 - - Germline - - - - - DNA SEQ - - FH - PubMed: Alonso 2009 - - - Spain ES - - - - 1 Sarah Leigh
+?/. - c.-120C>T r.(?) p.(=) - - - Unknown - likely pathogenic g.11200105C>T g.11089429C>T LDLR(NM_000527.5):c.-120C>T - LDLR_001115 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/+? 1 c.-101T>C r.(=) p.(=) TATA box 64% of WT promoter activity (luciferase assay) {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} conservation: 12/12 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - - - DNA SEQ - - FH - PubMed: Usifo 2012 - - - United Kingdom (Great Britain) Unknown - - - - 1 Sarah Leigh
?/. - c.-98C>T r.(?) p.(=) - - - Unknown - VUS g.11200127C>T g.11089451C>T LDLR(NM_000527.5):c.-98C>T - LDLR_001925 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/-? 1 c.-88G>A r.(=) p.(=) 5'UTR Normal levels of transcription (luciferase assay in HEPG2 cells) conservation: 12/12 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 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 - - - DNA PCR, SEQ peripheral blood - FH - PubMed: De Castro-Oros 2011 Proband from FH family, with CVD. No variants identified from Lipochip v3–v8 (Progenika Biopharma, Derio, Spain). LDL-C = 220 mg/dl - - Spain Spanish - - - - 1 Sarah Leigh
?/? 1 c.-68A>C r.(=) p.(=) 5'UTR not tested conservation: 5/11 conservation {PMID25248394:Khamis et al European Journal of Human Genetics (2015) 23, 790–795} Parent #1 ACGS VUS g.11200157A>C g.11089481A>C - - LDLR_001121 - PubMed: Laurie 2004 - - Germline - - - - - DNA SEQ - - FH - PubMed: Laurie 2004 - - - New Zealand European - - - - 1 Sarah Leigh
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