Variant detail

mut_id 324 · c.1787C>T · p.Ala596Val

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Evidence at a glance

9
Linked patients
9
Patient-variant records
11
Linked references
6
Countries reported
cTTP (9)
Common phenotype
compound_heterozygous (6)
Common zygosity

Summary

Point missense_variant Residue 596 AlphaMissense key A596V
HGVS
c.1787C>T
Protein change
p.Ala596Val
rsID
rs281875299
Location
exon 16
gnomAD AF
0.00000681
Domain
Spacer
Gene
ADAMTS13

External links

dbSNP

References

Congenital thrombotic thrombocytopenic purpura (TTP) with placental abruption despite maternal improvement: a case report
Authors: Soffer MD, Bendapudi PK, Roberts DJ, Edelson PK, Kuter DJ, Ecker JL, Bryant A, Goldfarb IT.
Source: BMC Pregnancy Childbirth (2020)
Citation: BMC Pregnancy Childbirth. 2020 Jun 15;20(1):365. doi: 10.1186/s12884-020-03051-2.
PubMed: 32539690 · DOI: 10.1186/s12884-020-03051-2
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
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
A novel homozygous frameshift mutation in Exon 7 of the ADAMTS13 gene in a patient with congenital thrombotic thrombocytopenic purpura from India: a case report
Authors: Yadav S, Shetty S, Kulkarni B.
Source: Transfusion (2017)
Citation: Transfusion. 2017 Nov;57(11):2712-2714. doi: 10.1111/trf.14279. Epub 2017 Aug 21.
PubMed: 28833243 · DOI: 10.1111/trf.14279
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
Prevalence of the ADAMTS-13 missense mutation R1060W in late onset adult thrombotic thrombocytopenic purpura
Authors: Camilleri RS, Cohen H, Mackie IJ, Scully M, Starke RD, Crawley JT, Lane DA, Machin SJ.
Source: J Thromb Haemost (2008)
Citation: J Thromb Haemost. 2008 Feb;6(2):331-8. doi: 10.1111/j.1538-7836.2008.02846.x. Epub 2007 Nov 20.
PubMed: 18031293 · DOI: 10.1111/j.1538-7836.2008.02846.x
An enzyme immunoassay of ADAMTS13 distinguishes patients with thrombotic thrombocytopenic purpura from normal individuals and carriers of ADAMTS13 mutations
Authors: Zhou W, Tsai HM.
Source: Thromb Haemost (2004)
Citation: Thromb Haemost. 2004 Apr;91(4):806-11. doi: 10.1160/TH03-11-0675.
PubMed: 15045144 · DOI: 10.1160/TH03-11-0675
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
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
Nonsense-mediated mRNA decay in the ADAMTS13 gene caused by a 29-nucleotide deletion
Authors: Garagiola I, Valsecchi C, Lavoretano S, Oren H, Bohm M, Peyvandi F.
Source: Haematologica (2008)
Citation: Haematologica. 2008 Nov;93(11):1678-85. doi: 10.3324/haematol.13102. Epub 2008 Oct 2.
PubMed: 18835837 · DOI: 10.3324/haematol.13102

Amino-acid property change

Residue substitution
A → V at 596
AlphaMissense score
0.7522
Likely pathogenic
CSV class: LPath
Hydrophobicity
hydrophobic → hydrophobic (unchanged)
Charge
neutral → neutral (unchanged)
Polarity
nonpolar → nonpolar (unchanged)
Size
small → medium
Residue type
aliphatic → aliphatic (unchanged)
Typical protein position
buried → buried (unchanged)
Hydropathy index
1.8 → 4.2
Molecular weight
89.1 → 117.1
Original residue details
A · alanine
code: Ala
hydro: hydrophobic
charge: neutral
polarity: nonpolar
size: small
type: aliphatic
Variant residue details
V · valine
code: Val
hydro: hydrophobic
charge: neutral
polarity: nonpolar
size: medium
type: aliphatic

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 596 highlighted in red.
AlphaFold Q76LX8 ADAMTS13 structure
Domain: Spacer
Domain colours match the homepage domain viewer.

Patient summary

Countries represented
UK (3); France (2); USA (1); China (1); Japan (1); Haiti (1)
Phenotype
cTTP (9)
Zygosity
compound_heterozygous (6); homozygous (3)
Sex
female (7); male (2)
Pregnancy-related
no (6); yes (2); unknown (1)
Triggers
none (4); unknown (2); pregnancy (2); infection (1)
Treatment
unknown (6); PI (2); on-demand Koate-DVI (1)
ADAMTS13 activity
n=8; median=5; range=0.5–5
Age of onset
n=7; median=1; range=1–29
Age of diagnosis
n=5; median=5; range=1–18
Platelet count
n=2; median=24; range=13–35

Variant fields

mut_syn_HGVS
c.1787C>T
cdna_numb_HGVS
1787
cdna_numb_legacy
1787
nt_change
C>T
n_bp
1
nuc_numb
1787
g_numb
g16
aa_numb_HGVS
596
aa_numb_legacy
596
aa_first
Ala
aa_last
Val
aa_syn
p.Ala596Val
codon_first
GCG
codon_last
GTG
gnomAD_AC
11
gnomAD_AN
1613954
gnomAD_AF
0.00000681
g_id
g16
g_name
ADAMTS13
comments
Pathogenic
refState
complete
ref_id
55, 72, 76, 87, 138, 161, 176, 205, 214, 239, 266, 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
21 324 277 55 cTTP compound_heterozygous USA female <1 <1 <5 13 no infection on-demand Koate-DVI
66 324 48 87 cTTP compound_heterozygous China female <1 5 <5 35 no unknown PI
158 324 50 214 cTTP compound_heterozygous Japan male <21 unknown <0.5 unknown unknown unknown unknown
184 324 326 239 cTTP compound_heterozygous UK female unknown unknown unknown unknown yes pregnancy unknown
241 324 . 266 cTTP homozygous France female unknown 8 <5 unknown no none unknown
264 324 75 176 cTTP compound_heterozygous France female <1 18 <5 unknown no none unknown
267 324 176 cTTP homozygous Haiti female <1 5 <5 unknown no none unknown
350 324 256 138 cTTP compound_heterozygous UK female 29 unknown <5 unknown yes pregnancy unknown
359 324 . 138 cTTP homozygous UK male 1 unknown <5 unknown no none PI