Variant detail

mut_id 273 · c.4143dupA · p.Glu1382ArgfsTer6

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Evidence at a glance

62
Linked patients
62
Patient-variant records
22
Linked references
12
Countries reported
cTTP (62)
Common phenotype
homozygous (31)
Common zygosity

Summary

Duplication frameshift_variant Pathogenic Residue 138 AlphaMissense key E138R
HGVS
c.4143dupA
Protein change
p.Glu1382ArgfsTer6
rsID
rs387906343
ClinVar ID
5807
GRCh38 coordinate
133459038
Location
exon 29
gnomAD AF
0.00005145
Domain
Metalloprotease
Gene
ADAMTS13

External links

dbSNP ClinVar gnomAD

References

[Advance in the diagnosis and treatment of hereditary thrombotic thrombocytopenic purpura]
Authors: Liu W, Xiao Y.
Source: Zhonghua Yi Xue Yi Chuan Xue Za Zhi (2022)
Citation: Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2022 Apr 10;39(4):442-446. doi: 10.3760/cma.j.cn511374-20200804-00585.
PubMed: 35446985 · DOI: 10.3760/cma.j.cn511374-20200804-00585
First reported case of congenital thrombotic thrombocytopenic purpura in Taiwan with novel mutation of ADAMTS13 gene
Authors: Chou SC, Lin DT, Lin CY, Huang YC, Hsieh HN, Shen MC.
Source: Int J Hematol (2021)
Citation: Int J Hematol. 2021 May;113(5):760-764. doi: 10.1007/s12185-020-03068-5. Epub 2021 Jan 2.
PubMed: 33387295 · DOI: 10.1007/s12185-020-03068-5
Inherited Thrombotic Thrombocytopenic Purpura Revealed by Recurrent Strokes in a Male Adult: Case Report and Literature Review
Authors: Beauvais D, Venditti L, Chassin O, Joly B, Ameri A, Boisseau P, Lambotte O, Coppo P, Veyradier A, Denier C.
Source: J Stroke Cerebrovasc Dis (2019)
Citation: J Stroke Cerebrovasc Dis. 2019 Jun;28(6):1537-1539. doi: 10.1016/j.jstrokecerebrovasdis.2019.03.011. Epub 2019 Mar 28.
PubMed: 30930238 · DOI: 10.1016/j.jstrokecerebrovasdis.2019.03.011
The International Hereditary Thrombotic Thrombocytopenic Purpura Registry: key findings at enrollment until 2017
Authors: van Dorland HA, Taleghani MM, Sakai K, Friedman KD, George JN, Hrachovinova I, Knöbl PN, von Krogh AS, Schneppenheim R, Aebi-Huber I, Bütikofer L, Largiadèr CR, Cermakova Z, Kokame K, Miyata T, Yagi H, Terrell DR, Vesely SK, Matsumoto M, Lämmle B, Fujimura Y, Kremer Hovinga JA; Hereditary TTP Registry.
Source: Haematologica (2019)
Citation: Haematologica. 2019 Oct;104(10):2107-2115. doi: 10.3324/haematol.2019.216796. Epub 2019 Feb 21.
PubMed: 30792199 · DOI: 10.3324/haematol.2019.216796
[Novel ADAMTS13 compound heterozygous mutation in a patient with hereditary thrombotic thrombocytopenic purpura]
Authors: Wang CY, Fang XY, Shen Q.
Source: Zhonghua Er Ke Za Zhi (2016)
Citation: Zhonghua Er Ke Za Zhi. 2016 May;54(5):387-8. doi: 10.3760/cma.j.issn.0578-1310.2016.05.017.
PubMed: 27143085 · DOI: 10.3760/cma.j.issn.0578-1310.2016.05.017
Congenital thrombotic thrombocytopenic purpura related to a novel mutation in ADAMTS13 gene and management during pregnancy
Authors: Epperla N, Hemauer K, Friedman KD, George JN, Foy P.
Source: Am J Hematol (2016)
Citation: Am J Hematol. 2016 Jun;91(6):644-6. doi: 10.1002/ajh.24311.
PubMed: 26822222 · DOI: 10.1002/ajh.24311
Low incidence of ADAMTS13 missense mutation R1060W in adult Egyptian patients with thrombotic thrombocytopenic purpura
Authors: El Sissy MH, El Hafez AA, El Sissy AH.
Source: Acta Haematol (2014)
Citation: Acta Haematol. 2014;132(1):30-5. doi: 10.1159/000355645. Epub 2013 Dec 31.
PubMed: 24401653 · DOI: 10.1159/000355645
ADAMTS13 activity and genetic mutations in Japan
Authors: Miyata T, Kokame K, Matsumoto M, Fujimura Y.
Source: Hamostaseologie (2013)
Citation: Hamostaseologie. 2013 May 29;33(2):131-7. doi: 10.5482/HAMO-12-11-0017.
PubMed: 23715102 · DOI: 10.5482/HAMO-12-11-0017
Upshaw-Schulman Syndrome
Authors: John BM, Singh D, Ravichander B, Madan R, Raghu Raman TS.
Source: Med J Armed Forces India (2010)
Citation: Med J Armed Forces India. 2010 Apr;66(2):188-9. doi: 10.1016/S0377-1237(10)80149-2. Epub 2011 Jul 21.
PubMed: 27375335 · DOI: 10.1016/S0377-1237(10)80149-2
Mutation of the H-bond acceptor S119 in the ADAMTS13 metalloprotease domain reduces secretion and substrate turnover in a patient with congenital thrombotic thrombocytopenic purpura
Authors: Feys HB, Pareyn I, Vancraenenbroeck R, De Maeyer M, Deckmyn H, Van Geet C, Vanhoorelbeke K.
Source: Blood (2009)
Citation: Blood. 2009 Nov 19;114(21):4749-52. doi: 10.1182/blood-2009-07-230615. Epub 2009 Sep 28.
PubMed: 19786614 · DOI: 10.1182/blood-2009-07-230615
In-vitro and in-vivo consequences of mutations in the von Willebrand factor cleaving protease ADAMTS13 in thrombotic thrombocytopenic purpura
Authors: Donadelli R, Banterla F, Galbusera M, Capoferri C, Bucchioni S, Gastoldi S, Nosari S, Monteferrante G, Ruggeri ZM, Bresin E, Scheiflinger F, Rossi E, Martinez C, Coppo R, Remuzzi G, Noris M; International Registry of Recurrent and Familial HUS/TTP.
Source: Thromb Haemost (2006)
Citation: Thromb Haemost. 2006 Oct;96(4):454-64.
PubMed: 17003922
Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome
Authors: Matsumoto M, Kokame K, Soejima K, Miura M, Hayashi S, Fujii Y, Iwai A, Ito E, Tsuji Y, Takeda-Shitaka M, Iwadate M, Umeyama H, Yagi H, Ishizashi H, Banno F, Nakagaki T, Miyata T, Fujimura Y.
Source: Blood (2004)
Citation: Blood. 2004 Feb 15;103(4):1305-10. doi: 10.1182/blood-2003-06-1796. Epub 2003 Oct 16.
PubMed: 14563640 · DOI: 10.1182/blood-2003-06-1796
Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13
Authors: Pimanda JE, Maekawa A, Wind T, Paxton J, Chesterman CN, Hogg PJ.
Source: Blood (2004)
Citation: Blood. 2004 Jan 15;103(2):627-9. doi: 10.1182/blood-2003-04-1346. Epub 2003 Sep 25.
PubMed: 14512317 · DOI: 10.1182/blood-2003-04-1346
Thrombotic thrombocytopenic purpura in a newborn
Authors: Jubinsky PT, Moraille R, Tsai HM.
Source: J Perinatol (2003)
Citation: J Perinatol. 2003 Jan;23(1):85-7. doi: 10.1038/sj.jp.7210853.
PubMed: 12556937 · DOI: 10.1038/sj.jp.7210853
Remission of thrombotic thrombocytopenic purpura in a patient with compound heterozygous deficiency of von Willebrand factor-cleaving protease by infusion of solvent/detergent plasma
Authors: Kentouche K, Budde U, Furlan M, Scharfe V, Schneppenheim R, Zintl F.
Source: Acta Paediatr (2002)
Citation: Acta Paediatr. 2002;91(10):1056-9. doi: 10.1080/080352502760311548.
PubMed: 12434890 · DOI: 10.1080/080352502760311548
Mutations and Common Polymorphisms in ADAMTS13 and vWF Genes Responsible for Increasing Risk of Thrombosis
Authors: Haybar H, Khodadi E, Kavianpour M, Saki N.
Source: Cardiovasc Hematol Disord Drug Targets (2018)
Citation: Cardiovasc Hematol Disord Drug Targets. 2018;18(3):176-181. doi: 10.2174/1871529X18666180419102214.
PubMed: 29669506 · DOI: 10.2174/1871529X18666180419102214
Congenital late onset thrombotic thrombocytopenic purpura: a diagnostic challenge
Authors: Enjeti AK, Chapman K, Taylor PJ, Meldrum C.
Source: Pathology (2015)
Citation: Pathology. 2015 Oct;47(6):585-6. doi: 10.1097/PAT.0000000000000303.
PubMed: 26352112 · DOI: 10.1097/PAT.0000000000000303
Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes
Authors: Scully M, Thomas M, Underwood M, Watson H, Langley K, Camilleri RS, Clark A, Creagh D, Rayment R, Mcdonald V, Roy A, Evans G, McGuckin S, Ni Ainle F, Maclean R, Lester W, Nash M, Scott R, O Brien P; collaborators of the UK TTP Registry.
Source: Blood (2014)
Citation: Blood. 2014 Jul 10;124(2):211-9. doi: 10.1182/blood-2014-02-553131. Epub 2014 May 23.
PubMed: 24859360 · DOI: 10.1182/blood-2014-02-553131
Effects of naturally occurring mutations in CUB-1 domain on synthesis, stability, and activity of ADAMTS-13
Authors: Zhou Z, Jing H, Tao Z, Choi H, Aboulfatova K, Moake J, Li R, Dong JF.
Source: Thromb Res (2009)
Citation: Thromb Res. 2009 Jul;124(3):323-7. doi: 10.1016/j.thromres.2008.09.007. Epub 2008 Nov 21.
PubMed: 19027144 · DOI: 10.1016/j.thromres.2008.09.007
Novel homozygous ADAMTS13 mutation with neonatal presentation of congenital thrombotic thrombocytopenic purpura in two Indian origin babies
Authors: Debaditya Das, Ming Wei Lee, Shivani Dogra, Bikramjit Das, Joyce Lam, Sudip Sengupta, Rajat Bhattacharyya
Source: Pediatric Hematology Oncology Journal (2019)
Citation: Pediatric Hematology Oncology Journal, Valume 4, Issue 1, 2019. Pages 27-29, ISSN 2468-1245
DOI: 10.1016/j.phoj.2018.12.001
PB0637 - A first care report of congenital thrombotic thrombocytopenic purpura (cTTP) in ADAMTS13 gene in Thailand
Source: ISTH 2024 (2024)
PubMed: ISTH 2024
PB1581 | Adult Onset Hereditary Thrombotic Thrombocytopenic Purpura (TTP) with a Novel ADAMTS13 Mutation
Authors: J.M. Freue 1 ; B. Rosales Ostriz 1 ; M. Martin 2 ; R.M. Campestri 1
Source: ISTH 2019 (2019)
Citation: ISTH2019
PubMed: ISTH 2019

Amino-acid property change

Residue substitution
E → R at 138
AlphaMissense score
0.1002
Likely benign
CSV class: LBen
Hydrophobicity
hydrophilic → hydrophilic (unchanged)
Charge
negative → postive
Polarity
polar → polar (unchanged)
Size
large → large (unchanged)
Residue type
acidic → basic
Typical protein position
surface → surface (unchanged)
Hydropathy index
-3.5 → -4.5
Molecular weight
147.1 → 174.2
Original residue details
E · glutamic acid
code: Glu
hydro: hydrophilic
charge: negative
polarity: polar
size: large
type: acidic
Variant residue details
R · arginine
code: Arg
hydro: hydrophilic
charge: postive
polarity: polar
size: large
type: basic

Interactive AlphaFold structure

Interactive local 3D view of the AlphaFold Q76LX8 ADAMTS13 structure.
Drag to rotate, shift-drag to move, and use the mouse wheel to zoom in and out. The default view shows the full ADAMTS13 structure, with residue 138 highlighted in red.
AlphaFold Q76LX8 ADAMTS13 structure
Domain: Metalloprotease
Domain colours match the homepage domain viewer.

Patient summary

Countries represented
Norway (20); Germany (14); Czech Republic (6); Poland (5); Turkey (4); Switzerland (4); Italy (4); Bosnia and Herzegovina (1); USA (1); Australia (1); Sweden (1); Hungary (1)
Phenotype
cTTP (62)
Zygosity
homozygous (31); compound_heterozygous (28); heterozygous (3)
Sex
female (33); male (25); unknown (4)
Pregnancy-related
no (34); unknown (18); yes (7)
Triggers
none (30); unknown (20); pregnancy (7); infection (4); alcohol (1)
Treatment
PI (25); unknown (21); none (9); PEX (4); on-demand PI (3)
ADAMTS13 activity
n=58; median=2; range=1–20
Age of onset
n=42; median=16.5; range=1–52
Age of diagnosis
n=33; median=28; range=1–60
Platelet count
n=13; median=32; range=11–140

Variant fields

mut_syn_HGVS
c.4143dupA
cdna_numb_HGVS
4143
cdna_numb_legacy
4143
nt_change
Duplication
n_bp
1
nuc_numb
4143
g_numb
g16
aa_numb_HGVS
138
aa_numb_legacy
138
aa_first
Glu
aa_last
Arg
aa_syn
p.Glu1382ArgfsTer6
codon_first
A
codon_last
AA
coordinate_GRCh38
133459038
gnomAD_AC
83
gnomAD_AN
1613066
gnomAD_AF
0.00005145
clinvar_id
5807
clinvar_classification
Pathogenic
g_id
g16
g_name
ADAMTS13
comments
Pathogenic
refState
complete
ref_id
31, 47, 71, 72, 93, 95, 116, 125, 149, 153, 164, 180, 181, 185, 186, 220, 233, 240, 265, 305, 307, 310, 330, 332

Patients linked by mut_id

patient_id mut_id compound_partner_mut_id ref_id phenotype zygosity country sex age_of_onset age_of_diagnosis ad13_activity platelet_count pregnancy_related triggers treatment
7 273 . 31 cTTP homozygous Bosnia and Herzegovina male 28 28 <6 11 no none PI
17 273 12 47 cTTP compound_heterozygous Turkey male 4 12 <1 18 no none PI
64 273 117 84 cTTP compound_heterozygous USA female 32 48 <5 60 unknown unknown unknown
70 273 343 95 cTTP compound_heterozygous Norway male 18 28 1.8 unknown no unknown PI
71 273 . 95 cTTP homozygous Norway female 27 36 <1 unknown unknown unknown none
72 273 . 95 cTTP homozygous Norway male 44 51 <1 unknown no unknown none
73 273 . 95 cTTP homozygous Norway female 49 57 <1 unknown unknown unknown none
74 273 . 95 cTTP homozygous Norway male 52 60 <1 unknown no unknown PI
75 273 . 95 cTTP homozygous Norway male 23 30 <1 unknown no unknown none
76 273 . 95 cTTP homozygous Norway female 23 unknown <1 unknown unknown unknown none
77 273 . 95 cTTP homozygous Norway male 24 29 <1 unknown no unknown none
79 273 133 95 cTTP compound_heterozygous Norway female 38 39 <1 unknown unknown unknown none
80 273 273 95 cTTP homozygous Norway male 25 31 <1 unknown no unknown PI
81 273 75 95 cTTP compound_heterozygous Norway female 48 59 <1 unknown unknown unknown PI
82 273 . 95 cTTP homozygous Norway female 34 45 1 unknown unknown unknown PI
83 273 . 95 cTTP homozygous Norway female 4 9 <1 unknown unknown unknown PI
84 273 . 95 cTTP homozygous Norway male 23 30 <1 unknown unknown unknown PI
88 273 . 116 cTTP homozygous Poland female 20 post-mortem unknown unknown yes pregnancy unknown
99 273 . 93 cTTP homozygous Switzerland male unknown unknown <1 unknown no unknown unknown
100 273 . 93 cTTP homozygous Switzerland male unknown unknown <1 unknown no alcohol unknown
101 273 . 93 cTTP homozygous Switzerland male unknown unknown <1 unknown no unknown unknown
102 273 75 93 cTTP compound_heterozygous Switzerland female unknown unknown <1 unknown unknown unknown unknown
113 273 339 125 cTTP compound_heterozygous Poland male unknown 52 unknown unknown no unknown unknown
114 273 . 125 cTTP homozygous Poland female unknown 16 unknown unknown no unknown PI
122 273 282 180 cTTP compound_heterozygous Australia female unknown 1 <10 unknown none on-demand PI
126 273 . 153 cTTP homozygous Czech Republic male unknown unknown 2 86 no none PEX
127 273 . 153 cTTP homozygous Czech Republic male unknown unknown 3 70 no none PEX
128 273 . 153 cTTP homozygous Czech Republic male unknown unknown 2 140 no none PEX
129 273 . 153 cTTP heterozygous Czech Republic female unknown unknown 3 30 unknown none PEX
130 273 . 153 cTTP heterozygous Czech Republic female unknown unknown <3 57 no none PI
131 273 . 153 cTTP heterozygous Czech Republic female unknown unknown <3 60 no none PI
132 273 . 154 cTTP homozygous Sweden male unknown 38 32 no none PI
191 273 . 240 cTTP homozygous Norway female unknown unknown <5 unknown yes pregnancy unknown
192 273 75 240 cTTP compound_heterozygous Norway female unknown unknown <5 unknown yes pregnancy unknown
193 273 . 240 cTTP homozygous Norway female unknown unknown <5 unknown yes pregnancy unknown
194 273 . 240 cTTP homozygous Norway female <1 21 <5 unknown yes pregnancy unknown
195 273 . 240 cTTP homozygous Norway female unknown 26 <5 unknown yes pregnancy unknown
196 273 133 240 cTTP compound_heterozygous Norway female 37 37 <5 unknown yes pregnancy unknown
200 273 . 233 cTTP homozygous Italy male 7 unknown <6 unknown no infection PI
201 273 339 233 cTTP compound_heterozygous Italy male 35 unknown <6 unknown no none PI
202 273 . 233 cTTP homozygous Italy female 3 unknown <6 unknown no infection PI
207 273 207 233 cTTP compound_heterozygous Italy male 15 20 <6 11 no infection PI
224 273 . 149 cTTP homozygous Poland female <1 18 <2 unknown no none none
225 273 . 149 cTTP homozygous Poland female <1 15 <2 unknown no none PI
236 273 12 265 cTTP compound_heterozygous Turkey male 15 20 <6 11 infection PI
237 273 12 265 cTTP compound_heterozygous Turkey female 22 22 <6 unknown none unknown
242 273 133 307 cTTP compound_heterozygous Hungary female 18 unknown <1 unknown no none unknown
245 273 39 305 cTTP compound_heterozygous Germany male <1 unknown <2 unknown no none on-demand PI
247 273 130 305 cTTP compound_heterozygous Germany female <1 16 <2 unknown no none PI
250 273 49 305 cTTP compound_heterozygous Germany male <1 10 <2 unknown no none none
251 273 347 305 cTTP compound_heterozygous Germany male 3 3 <2 unknown no none PI
282 273 371 330 cTTP compound_heterozygous Germany female 23 23 4 26 no none PI
292 273 130 185 cTTP compound_heterozygous Germany female <1 16 <1 unknown no none PI
295 273 12 310 cTTP compound_heterozygous Turkey male unknown unknown <20 unknown no none unknown
335 273 220 cTTP homozygous Germany female <1 unknown <5 unknown no none on-demand PI
336 273 . 220 cTTP homozygous Germany female unknown unknown <3 unknown unknown none unknown
337 273 306 220 cTTP compound_heterozygous Germany female <1 unknown <4 unknown unknown none PI
338 273 130 220 cTTP compound_heterozygous Germany female <1 unknown <2 unknown unknown none PI
341 273 295 186 cTTP compound_heterozygous Germany unknown <1 unknown <5 unknown unknown none unknown
343 273 130 186 cTTP compound_heterozygous Germany unknown <1 unknown <2 unknown unknown none unknown
346 273 49 186 cTTP compound_heterozygous Germany unknown 4 unknown <2 unknown unknown none unknown
347 273 347 186 cTTP compound_heterozygous Germany unknown 3 unknown <2 unknown unknown none unknown