Variant detail

mut_id 94 · c.2074C>T · p.Arg692Cys

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Evidence at a glance

8
Linked patients
8
Patient-variant records
11
Linked references
6
Countries reported
cTTP (8)
Common phenotype
homozygous (5)
Common zygosity

Summary

Point missense_variant Pathogenic Residue 692 AlphaMissense key R692C
HGVS
c.2074C>T
Protein change
p.Arg692Cys
rsID
rs121908475
ClinVar ID
5809
GRCh38 coordinate
133442504
Location
exon 17
gnomAD AF
6.82E-06
Domain
TSP type-1 2
Gene
ADAMTS13

External links

dbSNP ClinVar gnomAD

References

The challenging follow-up of pregnancy in women with known thrombotic thrombocytopenic purpura: a single-center experience of a preemptive management protocol
Authors: Hamroun A, Prouteau C, Lenain R, Roger C, Bauters A, Zawadzki C, Subtil D, Gibier JB, Stichelbout M, Coppo P, Lionet A, Maanaoui M, Hazzan M, Provôt F.
Source: J Nephrol (2023)
Citation: J Nephrol. 2023 Dec;36(9):2519-2529. doi: 10.1007/s40620-023-01790-x. Epub 2023 Oct 11.
PubMed: 37816989 · DOI: 10.1007/s40620-023-01790-x
Hereditary Thrombotic Thrombocytopenic Purpura in a 9-Month-old: Diagnosing and Managing an Ultra-rare Disorder
Authors: Wyatt KD, Kohorst MA, Coon LM, Hurley RM, van Dorland HA, Arndt CAS.
Source: J Pediatr Hematol Oncol (2021)
Citation: J Pediatr Hematol Oncol. 2021 May 1;43(4):e577-e579. doi: 10.1097/MPH.0000000000001830.
PubMed: 32496441 · DOI: 10.1097/MPH.0000000000001830
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
A Rare Case of Thrombotic Thrombocytopenic Purpura Caused by Pancreatitis and Clopidogrel
Authors: Rawala MS, Naqvi STS, Khan MY, El Toukhy A.
Source: Am J Case Rep (2018)
Citation: Am J Case Rep. 2018 Oct 30;19:1288-1291. doi: 10.12659/AJCR.911679.
PubMed: 30374015 · DOI: 10.12659/AJCR.911679
Complement activation associated with ADAMTS13 deficiency may contribute to the characteristic glomerular manifestations in Upshaw-Schulman syndrome
Authors: Itami H, Hara S, Matsumoto M, Imamura S, Kanai R, Nishiyama K, Ishimura M, Ohga S, Yoshida M, Tanaka R, Ogawa Y, Asada Y, Sekita-Hatakeyama Y, Hatakeyama K, Ohbayashi C.
Source: Thromb Res (2018)
Citation: Thromb Res. 2018 Oct;170:148-155. doi: 10.1016/j.thromres.2018.08.020. Epub 2018 Sep 1.
PubMed: 30195146 · DOI: 10.1016/j.thromres.2018.08.020
[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
Hereditary thrombotic purpura
Authors: Khan MR, Ashraf MS.
Source: J Pak Med Assoc (2014)
Citation: J Pak Med Assoc. 2014 Feb;64(2):217-9.
PubMed: 24640819
Modulation of ADAMTS13 secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation
Authors: Plaimauer B, Fuhrmann J, Mohr G, Wernhart W, Bruno K, Ferrari S, Konetschny C, Antoine G, Rieger M, Scheiflinger F.
Source: Blood (2006)
Citation: Blood. 2006 Jan 1;107(1):118-25. doi: 10.1182/blood-2005-06-2482. Epub 2005 Sep 13.
PubMed: 16160007 · DOI: 10.1182/blood-2005-06-2482
Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity
Authors: Kokame K, Matsumoto M, Soejima K, Yagi H, Ishizashi H, Funato M, Tamai H, Konno M, Kamide K, Kawano Y, Miyata T, Fujimura Y.
Source: Proc Natl Acad Sci U S A (2002)
Citation: Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11902-7. doi: 10.1073/pnas.172277399. Epub 2002 Aug 14.
PubMed: 12181489 · DOI: 10.1073/pnas.172277399
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
Genotype–Phenotype Variability in Congenital Thrombotic Thrombocytopenic Purpura (TTP): Two Novel ADAMTS13 Variants
Authors: Radhakrishnan N, Pandharipande A S, Gaire H, et al.
Source: Cureus (2025)
Citation: Cureus 17(11): e97714
PubMed: 41458739 · DOI: 10.7759/cureus.97714

Amino-acid property change

Residue substitution
R → C at 692
AlphaMissense score
0.3713
Uncertain
CSV class: Amb
Hydrophobicity
hydrophilic → hydrophilic (unchanged)
Charge
postive → neutral
Polarity
polar → polar (unchanged)
Size
large → medium
Residue type
basic → Unknown
Typical protein position
surface → buried
Hydropathy index
-4.5 → 2.5
Molecular weight
174.2 → 121.2
Original residue details
R · arginine
code: Arg
hydro: hydrophilic
charge: postive
polarity: polar
size: large
type: basic
Variant residue details
C · cysteine
code: Cys
hydro: hydrophilic
charge: neutral
polarity: polar
size: medium
type:

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 692 highlighted in red.
AlphaFold Q76LX8 ADAMTS13 structure
Domain: TSP type-1 2
Domain colours match the homepage domain viewer.

Patient summary

Countries represented
China (2); El Salvador (2); USA (1); Switzerland (1); Canada (1); Portugal (1)
Phenotype
cTTP (8)
Zygosity
homozygous (5); compound_heterozygous (3)
Sex
female (6); male (2)
Pregnancy-related
no (4); yes (2); unknown (2)
Triggers
none (4); pregnancy (2); unknown (1); infection (1)
Treatment
unknown (4); PI (4)
ADAMTS13 activity
n=8; median=5; range=1–33
Age of onset
n=6; median=2.5; range=1–22
Age of diagnosis
n=4; median=4; range=1–33
Platelet count
n=2; median=27; range=13–41

Variant fields

mut_syn_HGVS
c.2074C>T
cdna_numb_HGVS
2074
cdna_numb_legacy
2074
nt_change
C>T
n_bp
1
nuc_numb
2074
g_numb
g16
aa_numb_HGVS
692
aa_numb_legacy
692
aa_first
Arg
aa_last
Cys
aa_syn
p.Arg692Cys
codon_first
CGT
codon_last
TGT
coordinate_GRCh38
133442504
gnomAD_AC
11
gnomAD_AN
1613556
gnomAD_AF
6.82E-06
clinvar_id
5809
clinvar_classification
Pathogenic
g_id
g16
g_name
ADAMTS13
comments
Pathogenic
refState
complete
ref_id
13, 56, 71, 76, 78, 93, 114, 171, 188, 317, 319

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
3 94 99 13 cTTP compound_heterozygous China female 22 33 33 13 yes pregnancy unknown
22 94 264 56 cTTP compound_heterozygous USA female 16 6 41 no none unknown
86 94 . 114 cTTP homozygous El Salvador female 1 2 <1 unknown unknown none PI
87 94 . 114 cTTP homozygous El Salvador male <1 6 <1 unknown no none PI
104 94 211 93 cTTP compound_heterozygous Switzerland female unknown unknown <3 unknown unknown unknown unknown
290 94 . 319 cTTP homozygous China female unknown unknown <5 unknown yes pregnancy unknown
312 94 . 171 cTTP homozygous Canada female <1 <1 <5 unknown no none PI
314 94 . 78 cTTP homozygous Portugal male 4 unknown <10 unknown no infection PI