Variant detail

mut_id 133 · c.3178C>T · p.Arg1060Trp

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Evidence at a glance

57
Linked patients
57
Patient-variant records
30
Linked references
14
Countries reported
cTTP (57)
Common phenotype
compound_heterozygous (40)
Common zygosity

Summary

Point missense_variant Pathogenic/Likely pathogenic Residue 1060 AlphaMissense key R1060W
HGVS
c.3178C>T
Protein change
p.Arg1060Trp
rsID
rs142572218
ClinVar ID
68815
GRCh38 coordinate
133454548
Location
exon 24
gnomAD AF
0.001095
Domain
TSP type-1 7
Gene
ADAMTS13

External links

dbSNP ClinVar gnomAD

References

NEPHRO-ZEBRA-a neonate with severe jaundice, persistent thrombocytopenia & recurrent acute kidney injury later in childhood: Joining the dots!
Authors: Sethi SK, Yadav SP, Moideen A, Raina R.
Source: J Nephrol (2024)
Citation: J Nephrol. 2024 Apr;37(3):827-829. doi: 10.1007/s40620-023-01848-w. Epub 2024 Jan 25.
PubMed: 38267796 · DOI: 10.1007/s40620-023-01848-w
Congenital Thrombotic Thrombocytopenic Purpura: A Rare Cause of Recurrent Thrombocytopenia and Anemia
Authors: Assiri M, AlMalki A, AlHunif B, AlMofareh M.
Source: Cureus (2023)
Citation: Cureus. 2023 Sep 10;15(9):e44988. doi: 10.7759/cureus.44988. eCollection 2023 Sep.
PubMed: 37822445 · DOI: 10.7759/cureus.44988
Hereditary thrombotic thrombocytopenic purpura acquired through liver transplantation: A case report
Authors: Martin KA, Zakarija A, Odetola O, Simpson D, Cheung A, Kinsella E, Nadig S, Caicedo J, Stein R.
Source: Am J Transplant (2023)
Citation: Am J Transplant. 2023 Mar;23(3):437-439. doi: 10.1016/j.ajt.2022.11.026. Epub 2023 Jan 12.
PubMed: 36695683 · DOI: 10.1016/j.ajt.2022.11.026
Hypercoagulability and Inflammatory Markers in a Case of Congenital Thrombotic Thrombocytopenic Purpura Complicated by Fetal Demise
Authors: Skeith L, Hurd K, Chaturvedi S, Chow L, Nicholas J, Lee A, Young D, Goodyear D, Soucie J, Girard L, Dufour A, Agbani EO.
Source: J Clin Med (2022)
Citation: J Clin Med. 2022 Nov 30;11(23):7115. doi: 10.3390/jcm11237115.
PubMed: 36498688 · DOI: 10.3390/jcm11237115
A Case Report of Congenital Thrombotic Thrombocytopenic Purpura: The Peripheral Blood Smear Lights the Diagnosis
Authors: Toret E, Demir-Kolsuz O, Ozdemir ZC, Bor O.
Source: J Pediatr Hematol Oncol (2022)
Citation: J Pediatr Hematol Oncol. 2022 Jan 1;44(1):e243-e245. doi: 10.1097/MPH.0000000000002032.
PubMed: 33306605 · DOI: 10.1097/MPH.0000000000002032
Frequency and severity of pregnancy complications in women with hereditary thrombotic thrombocytopenic purpura
Authors: Kasht R, Borogovac A, George JN.
Source: Am J Hematol (2020)
Citation: Am J Hematol. 2020 Nov;95(11):E316-E318. doi: 10.1002/ajh.25964. Epub 2020 Sep 5.
PubMed: 32808675 · DOI: 10.1002/ajh.25964
Hereditary Thrombotic Thrombocytopenic Purpura
Authors: Kremer Hovinga JA, George JN.
Source: N Engl J Med (2019)
Citation: N Engl J Med. 2019 Oct 24;381(17):1653-1662. doi: 10.1056/NEJMra1813013.
PubMed: 31644845 · DOI: 10.1056/NEJMra1813013
Blood film says it all! Rare case of congenital TTP misdiagnosed as ITP
Authors: Majeed Memon A, Ali N.
Source: Int J Pediatr Adolesc Med (2019)
Citation: Int J Pediatr Adolesc Med. 2019 Jun;6(2):58-60. doi: 10.1016/j.ijpam.2019.02.005. Epub 2019 Feb 20.
PubMed: 31388548 · DOI: 10.1016/j.ijpam.2019.02.005
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
Genetic variations in complement factors in patients with congenital thrombotic thrombocytopenic purpura with renal insufficiency
Authors: Fan X, Kremer Hovinga JA, Shirotani-Ikejima H, Eura Y, Hirai H, Honda S, Kokame K, Taleghani MM, von Krogh AS, Yoshida Y, Fujimura Y, Lämmle B, Miyata T.
Source: Int J Hematol (2016)
Citation: Int J Hematol. 2016 Mar;103(3):283-91. doi: 10.1007/s12185-015-1933-7. Epub 2016 Feb 1.
PubMed: 26830967 · DOI: 10.1007/s12185-015-1933-7
The D173G mutation in ADAMTS-13 causes a severe form of congenital thrombotic thrombocytopenic purpura. A clinical, biochemical and in silico study
Authors: Lancellotti S, Peyvandi F, Pagliari MT, Cairo A, Abdel-Azeim S, Chermak E, Lazzareschi I, Mastrangelo S, Cavallo L, Oliva R, De Cristofaro R.
Source: Thromb Haemost (2016)
Citation: Thromb Haemost. 2016 Jan;115(1):51-62. doi: 10.1160/TH15-02-0119. Epub 2015 Aug 13.
PubMed: 26272487 · DOI: 10.1160/TH15-02-0119
Congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome) caused by novel ADAMTS13 mutations
Authors: Kim HY, Lee KO, Yoo KH, Kim SH, Oh D, Kim HJ.
Source: Br J Haematol (2016)
Citation: Br J Haematol. 2016 Apr;173(1):156-9. doi: 10.1111/bjh.13564. Epub 2015 Jun 18.
PubMed: 26085195 · DOI: 10.1111/bjh.13564
Development of a clinically significant ADAMTS13 inhibitor in a patient with hereditary thrombotic thrombocytopenic purpura
Authors: Raval JS, Padmanabhan A, Kremer Hovinga JA, Kiss JE.
Source: Am J Hematol (2015)
Citation: Am J Hematol. 2015 Jan;90(1):E22. doi: 10.1002/ajh.23851. Epub 2014 Oct 18.
PubMed: 25219856 · DOI: 10.1002/ajh.23851
Transfusion-dependent anaemia of undetermined origin: a distinctive syndrome in paediatric medical tourism
Authors: Lee AC.
Source: Ann Acad Med Singap (2012)
Citation: Ann Acad Med Singap. 2012 Jul;41(7):305-8.
PubMed: 22892608
A phenotype-genotype correlation of ADAMTS13 mutations in congenital thrombotic thrombocytopenic purpura patients treated in the United Kingdom
Authors: Camilleri RS, Scully M, Thomas M, Mackie IJ, Liesner R, Chen WJ, Manns K, Machin SJ.
Source: J Thromb Haemost (2012)
Citation: J Thromb Haemost. 2012 Sep;10(9):1792-801. doi: 10.1111/j.1538-7836.2012.04852.x.
PubMed: 22783805 · DOI: 10.1111/j.1538-7836.2012.04852.x
Natural history of Upshaw-Schulman syndrome based on ADAMTS13 gene analysis in Japan
Authors: Fujimura Y, Matsumoto M, Isonishi A, Yagi H, Kokame K, Soejima K, Murata M, Miyata T.
Source: J Thromb Haemost (2011)
Citation: J Thromb Haemost. 2011 Jul;9 Suppl 1:283-301. doi: 10.1111/j.1538-7836.2011.04341.x.
PubMed: 21781265 · DOI: 10.1111/j.1538-7836.2011.04341.x
A first case of congenital TTP on the African continent due to a new homozygous mutation in the catalytic domain of ADAMTS13
Authors: Meyer SC, Jeddi R, Meddeb B, Gouider E, Lämmle B, Kremer Hovinga JA.
Source: Ann Hematol (2008)
Citation: Ann Hematol. 2008 Aug;87(8):663-6. doi: 10.1007/s00277-008-0496-6. Epub 2008 Apr 29.
PubMed: 18443791 · DOI: 10.1007/s00277-008-0496-6
[Thrombotic thrombocytopenic purpura in a newborn]
Authors: Sudour H, Rouabah M, Mansuy L, Bordigoni P, Hascoet JM.
Source: Arch Pediatr (2007)
Citation: Arch Pediatr. 2007 Jan;14(1):39-42. doi: 10.1016/j.arcped.2006.10.016. Epub 2006 Nov 28.
PubMed: 17137768 · DOI: 10.1016/j.arcped.2006.10.016
A common origin of the 4143insA ADAMTS13 mutation
Authors: Schneppenheim R, Kremer Hovinga JA, Becker T, Budde U, Karpman D, Brockhaus W, Hrachovinová I, Korczowski B, Oyen F, Rittich S, von Rosen J, Tjønnfjord GE, Pimanda JE, Wienker TF, Lämmle B.
Source: Thromb Haemost (2006)
Citation: Thromb Haemost. 2006 Jul;96(1):3-6. doi: 10.1160/TH05-12-0817.
PubMed: 16807643 · DOI: 10.1160/TH05-12-0817
Recurrent C3 Glomerulonephritis with an ADAMTS 13 Gene Variant: A Case Report and Literature Review
Authors: Zahrani RAA, Nazmi AMAY, Hussain TOA.
Source: Saudi J Kidney Dis Transpl (2021)
Citation: Saudi J Kidney Dis Transpl. 2021 Nov-Dec;32(6):1782-1789. doi: 10.4103/1319-2442.352441.
PubMed: 35946293 · DOI: 10.4103/1319-2442.352441
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
ADAMTS genes and the risk of cerebral aneurysm
Authors: Arning A, Jeibmann A, Köhnemann S, Brokinkel B, Ewelt C, Berger K, Wellmann J, Nowak-Göttl U, Stummer W, Stoll M, Holling M.
Source: J Neurosurg (2016)
Citation: J Neurosurg. 2016 Aug;125(2):269-74. doi: 10.3171/2015.7.JNS154. Epub 2016 Jan 8.
PubMed: 26745484 · DOI: 10.3171/2015.7.JNS154
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
ADAMTS13 and its variants promote angiogenesis via upregulation of VEGF and VEGFR2
Authors: Lee M, Keener J, Xiao J, Long Zheng X, Rodgers GM.
Source: Cell Mol Life Sci (2015)
Citation: Cell Mol Life Sci. 2015 Jan;72(2):349-56. doi: 10.1007/s00018-014-1667-3. Epub 2014 Jun 21.
PubMed: 24950743 · DOI: 10.1007/s00018-014-1667-3
PB0637 - A first care report of congenital thrombotic thrombocytopenic purpura (cTTP) in ADAMTS13 gene in Thailand
Source: ISTH 2024 (2024)
PubMed: ISTH 2024
PB0849 | TTP during Pregnancy: Acquired or Late- Onset Congenital? A Diagnostic Challenge
Authors: S. Demeester ; N. De Beule; C. Orlando; A. De Becker; K. Jochmans
Source: ISTH 2021 (2021)
Citation: ISTH 2021
PubMed: ISTH 2021
Novel ADAMTS13 Mutation in a Patient With Congenital TTP Diagnosed in Pregnancy
Authors: Mawalla WF, Chamba C, Nasser A, Jonathan I, Josephat E, Yonazi M, Yusuph Z, Bresin E, Remuzzi G, Luzzatto L
Source: Am J Hematol. (2025)
Citation: Am J Hematol. 2025 Jul 11. doi: 10.1002/ajh.70007
PubMed: 40643312 · DOI: 10.1002/ajh.70007
Exome sequencing for diagnosis of congenital hemolytic anemia
Authors: Mansour-Hendili L, Aissat A, Badaoui B, Sakka M, Gameiro C, Ortonne V, Wagner-Ballon O, Pissard S, Picard V, Ghazal K, Bahuau M, Guitton C, Mansour Z, Duplan M, Petit A, Costedoat-Chalumeau N, Michel M, Bartolucci P, Moutereau S, Funalot B, Galactéros F
Source: Orphanet J Rare Dis (2020)
Citation: Orphanet J Rare Dis. 2020 Jul 8;15(1):180
PubMed: 32641076 · DOI: 10.1186/s13023-020-01425-5.
Characterization of autopsy findings including multivisceral glomeruloid vascular bodies in hereditary thrombotic thrombocytopenic purpura with two new variants in ADAMTS13 gene
Authors: Maragliano R, Perrot A, Loget P, Combescure C, Belhomme N, Faoucher M, Dubourg C, Fradin M, Collardeau-Frachon S
Source: Virchows Arch (2025)
Citation: Virchows Arch. 2025 Aug 4. doi: 10.1007/s00428-025-04200-8
PubMed: 40760196 · DOI: 10.1007/s00428-025-04200-8

Amino-acid property change

Residue substitution
R → W at 1060
AlphaMissense score
0.1158
Likely benign
CSV class: LBen
Hydrophobicity
hydrophilic → hydrophobic
Charge
postive → neutral
Polarity
polar → nonpolar
Size
large → large (unchanged)
Residue type
basic → aromatic
Typical protein position
surface → buried
Hydropathy index
-4.5 → -0.9
Molecular weight
174.2 → 204.2
Original residue details
R · arginine
code: Arg
hydro: hydrophilic
charge: postive
polarity: polar
size: large
type: basic
Variant residue details
W · tryptophan
code: Trp
hydro: hydrophobic
charge: neutral
polarity: nonpolar
size: large
type: aromatic

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 1060 highlighted in red.
AlphaFold Q76LX8 ADAMTS13 structure
Domain: TSP type-1 7
Domain colours match the homepage domain viewer.

Patient summary

Countries represented
UK (23); France (7); Switzerland (7); USA (4); Norway (4); Sweden (2); Germany (2); Australia (2); Netherlands (1); Spain (1); Italy (1); Russia (1)
Phenotype
cTTP (57)
Zygosity
compound_heterozygous (40); homozygous (15); heterozygous (2)
Sex
female (51); male (6)
Pregnancy-related
yes (44); no (10); unknown (3)
Triggers
pregnancy (43); unknown (6); none (6); quetiapine (1); infection (1)
Treatment
unknown (34); PI (16); on-demand PI (3); none (3); TAK (1)
ADAMTS13 activity
n=40; median=5; range=1–21
Age of onset
n=26; median=29.5; range=2–39
Age of diagnosis
n=22; median=34; range=19–70
Platelet count
n=10; median=28; range=6–69

Variant fields

mut_syn_HGVS
c.3178C>T
cdna_numb_HGVS
3178
cdna_numb_legacy
3178
nt_change
C>T
n_bp
1
nuc_numb
3178
g_numb
g16
aa_numb_HGVS
1060
aa_numb_legacy
1060
aa_first
Arg
aa_last
Trp
aa_syn
p.Arg1060Trp
codon_first
CGG
codon_last
TGG
coordinate_GRCh38
133454548
gnomAD_AC
1761
gnomAD_AN
1608810
gnomAD_AF
0.001095
clinvar_id
68815
clinvar_classification
Pathogenic/Likely pathogenic
g_id
g16
g_name
ADAMTS13
comments
Pathogenic
refState
complete
ref_id
7, 12, 21, 23, 48, 54, 66, 69, 71, 72, 94, 101, 103, 110, 138, 139, 145, 160, 163, 165, 197, 220, 232, 233, 239, 307, 308, 314, 316, 317, 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
5 133 . 23 cTTP heterozygous UK female unknown unknown 21 6 yes pregnancy PI
20 133 . 54 cTTP compound_heterozygous USA female 31 31 <5 19 yes pregnancy PI
44 133 . 66 cTTP homozygous UK female 30 70 8.5 49 yes pregnancy PI
47 133 343 69 cTTP compound_heterozygous Sweden female 15 29 <4 69 no quetiapine PI
52 133 265 101 cTTP compound_heterozygous Netherlands male 39 49 <1 31 no unknown PI
56 133 . 103 cTTP compound_heterozygous France female 24 24 5 25 yes pregnancy on-demand PI
61 133 4 110 cTTP compound_heterozygous Germany female 19 56 <10 unknown yes unknown unknown
67 133 59 94 cTTP compound_heterozygous USA female 19 19 <5 13 yes pregnancy PI
78 133 286 95 cTTP compound_heterozygous Norway male 38 44 5.3 unknown no unknown PI
79 133 273 95 cTTP compound_heterozygous Norway female 38 39 <1 unknown unknown unknown none
106 133 24 93 cTTP compound_heterozygous Switzerland female unknown unknown 5 unknown unknown unknown unknown
107 133 286 93 cTTP compound_heterozygous Switzerland male unknown unknown 5.3 unknown no unknown unknown
167 133 49 232 cTTP compound_heterozygous Australia female 30 46 <1 unknown unknown none PI
168 133 317 239 cTTP compound_heterozygous UK female unknown unknown unknown unknown yes pregnancy unknown
169 133 317 239 cTTP compound_heterozygous UK female unknown unknown unknown unknown yes pregnancy unknown
172 133 158 239 cTTP compound_heterozygous UK female unknown unknown unknown unknown yes pregnancy unknown
174 133 40 239 cTTP compound_heterozygous UK female unknown unknown unknown unknown yes pregnancy unknown
175 133 . 239 cTTP homozygous UK female unknown unknown unknown unknown yes pregnancy unknown
176 133 . 239 cTTP homozygous UK female unknown unknown unknown unknown yes pregnancy unknown
177 133 . 239 cTTP homozygous UK female unknown unknown unknown unknown yes pregnancy unknown
178 133 259 239 cTTP compound_heterozygous UK female unknown unknown unknown unknown yes pregnancy unknown
179 133 . 239 cTTP homozygous UK female unknown unknown unknown unknown yes pregnancy unknown
180 133 311 239 cTTP compound_heterozygous UK female unknown unknown unknown unknown yes pregnancy unknown
181 133 15 239 cTTP compound_heterozygous UK female unknown unknown unknown unknown yes pregnancy unknown
182 133 318 239 cTTP compound_heterozygous UK female unknown unknown unknown unknown yes pregnancy unknown
185 133 245 239 cTTP compound_heterozygous UK female unknown unknown unknown unknown yes pregnancy unknown
186 133 . 239 cTTP homozygous UK female unknown unknown unknown unknown yes pregnancy unknown
187 133 165 239 cTTP compound_heterozygous UK female unknown unknown unknown unknown yes pregnancy unknown
188 133 . 239 cTTP homozygous UK female unknown unknown unknown unknown yes pregnancy unknown
190 133 283 239 cTTP compound_heterozygous UK female unknown unknown unknown unknown yes pregnancy unknown
196 133 273 240 cTTP compound_heterozygous Norway female 37 37 <5 unknown yes pregnancy unknown
197 133 . 240 cTTP homozygous Norway female 31 31 <5 unknown yes pregnancy unknown
211 133 375 233 cTTP compound_heterozygous Spain female 20 unknown <6 unknown yes pregnancy unknown
212 133 375 233 cTTP compound_heterozygous Italy female 28 unknown <6 unknown yes pregnancy unknown
216 133 . 308 cTTP heterozygous USA female 34 34 6 55 yes pregnancy PI
219 133 332 21 cTTP compound_heterozygous Switzerland female 26 27 3.9 40 yes pregnancy TAK
221 133 . 145 cTTP homozygous Sweden female 26 34 <5 unknown yes pregnancy PI
226 133 53 197 cTTP compound_heterozygous Russia female 29 32 <10 19 yes pregnancy none
242 133 273 307 cTTP compound_heterozygous Hungary female 18 unknown <1 unknown no none unknown
262 133 221 165 cTTP compound_heterozygous USA male 34 unknown <5 unknown no none PI
286 133 37 314 cTTP compound_heterozygous Australia female 24 24 5.5 unknown yes pregnancy PI
288 133 2 316 cTTP compound_heterozygous Belgium female 31 31 3 unknown yes pregnancy PI
297 133 . 12 cTTP homozygous France female unknown unknown 8 unknown yes pregnancy unknown
298 133 49 12 cTTP compound_heterozygous France female unknown unknown 6 unknown yes pregnancy unknown
299 133 117 12 cTTP compound_heterozygous France female unknown unknown 9 unknown yes pregnancy unknown
300 133 . 12 cTTP homozygous France female unknown unknown 6 unknown yes pregnancy unknown
301 133 69 12 cTTP compound_heterozygous France female unknown unknown 9 unknown yes pregnancy unknown
303 133 . 12 cTTP homozygous France female unknown unknown 8 unknown yes pregnancy unknown
330 133 293 220 cTTP compound_heterozygous Germany female unknown unknown <5 unknown yes pregnancy on-demand PI
339 133 . 160 cTTP homozygous UK female 33 unknown <5 unknown yes pregnancy PI
348 133 . 138 cTTP homozygous UK female 33 unknown <5 unknown yes pregnancy unknown
349 133 40 138 cTTP compound_heterozygous UK female 23 unknown <5 unknown yes pregnancy unknown
363 133 283 138 cTTP compound_heterozygous UK female 2 unknown <5 unknown no infection on-demand PI
368 133 24 48 cTTP compound_heterozygous Switzerland female unknown 34 <1 unknown no none PI
369 133 . 48 cTTP homozygous Switzerland male unknown 61 1.8 unknown no none unknown
370 133 259 48 cTTP compound_heterozygous Switzerland male unknown 57 <1 unknown no none PI
371 133 58 48 cTTP compound_heterozygous Switzerland female unknown 27 <1 unknown yes pregnancy none