Variant detail

mut_id 312 · c.1225C>T · p.Arg409Trp

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Evidence at a glance

2
Linked patients
2
Patient-variant records
5
Linked references
2
Countries reported
cTTP (2)
Common phenotype
compound_heterozygous (1)
Common zygosity

Summary

Point missense_variant Uncertain significance Residue 409 AlphaMissense key R409W
HGVS
c.1225C>T
Protein change
p.Arg409Trp
rsID
rs959872423
ClinVar ID
1406149
GRCh38 coordinate
133433510
Location
exon 10
gnomAD AF
0.00000433
Domain
TSP type-1 1
Gene
ADAMTS13

External links

dbSNP ClinVar gnomAD

References

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
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
Application of high-throughput sequencing for hereditary thrombocytopenia in southwestern China
Authors: Zhang L, Yu J, Xian Y, Wen X, Guan X, Guo Y, Luo M, Dou Y.
Source: J Clin Lab Anal (2021)
Citation: J Clin Lab Anal. 2021 Aug;35(8):e23896. doi: 10.1002/jcla.23896. Epub 2021 Jul 8.
PubMed: 34237177 · DOI: 10.1002/jcla.23896
A Single Synonymous Variant (c.354G>A [p.P118P]) in ADAMTS13 Confers Enhanced Specific Activity
Authors: Hunt R, Hettiarachchi G, Katneni U, Hernandez N, Holcomb D, Kames J, Alnifaidy R, Lin B, Hamasaki-Katagiri N, Wesley A, Kafri T, Morris C, Bouché L, Panico M, Schiller T, Ibla J, Bar H, Ismail A, Morris H, Komar A, Kimchi-Sarfaty C.
Source: Int J Mol Sci (2019)
Citation: Int J Mol Sci. 2019 Nov 15;20(22):5734. doi: 10.3390/ijms20225734.
PubMed: 31731663 · DOI: 10.3390/ijms20225734
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 409
AlphaMissense score
0.6873
Likely pathogenic
CSV class: LPath
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 409 highlighted in red.
AlphaFold Q76LX8 ADAMTS13 structure
Domain: TSP type-1 1
Domain colours match the homepage domain viewer.

Patient summary

Countries represented
Japan (1); UK (1)
Phenotype
cTTP (2)
Zygosity
compound_heterozygous (1); homozygous (1)
Sex
female (1); male (1)
Pregnancy-related
unknown (1); no (1)
Triggers
unknown (1); none (1)
Treatment
unknown (1); PI (1)
ADAMTS13 activity
n=2; median=2.75; range=0.5–5
Age of onset
n=2; median=9.5; range=1–18
Age of diagnosis
Not available
Platelet count
n=1; median=33; range=33–33

Variant fields

mut_syn_HGVS
c.1225C>T
cdna_numb_HGVS
1225
cdna_numb_legacy
1225
nt_change
C>T
n_bp
1
nuc_numb
1225
g_numb
g16
aa_numb_HGVS
409
aa_numb_legacy
409
aa_first
Arg
aa_last
Trp
aa_syn
p.Arg409Trp
codon_first
CGG
codon_last
TGG
coordinate_GRCh38
133433510
gnomAD_AC
7
gnomAD_AN
1613404
gnomAD_AF
0.00000433
clinvar_id
1406149
clinvar_classification
Uncertain significance
g_id
g16
g_name
ADAMTS13
comments
Uncertain significance
refState
complete
ref_id
72, 138, 205, 214, 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
155 312 323 214 cTTP compound_heterozygous Japan female <18 unknown <0.5 33 unknown unknown unknown
354 312 . 138 cTTP homozygous UK male <1 unknown <5 unknown no none PI