Variant detail

mut_id 332 · c.2017A>T · p.Ile673Phe

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Evidence at a glance

7
Linked patients
7
Patient-variant records
7
Linked references
2
Countries reported
cTTP (7)
Common phenotype
compound_heterozygous (7)
Common zygosity

Summary

Point missense_variant Residue 673 AlphaMissense key I673F
HGVS
c.2017A>T
Protein change
p.Ile673Phe
rsID
rs281875307
Location
exon 17
gnomAD AF
0.00000681
Domain
Spacer
Gene
ADAMTS13

External links

dbSNP

References

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
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
[From gene to disease; congenital thrombotic thrombocytopenic purpura due to mutations in the ADAMTS13 gene]
Authors: Schiphorst RH, van de Kar NC, van den Heuvel LP.
Source: Ned Tijdschr Geneeskd (2003)
Citation: Ned Tijdschr Geneeskd. 2003 Dec 6;147(49):2422-4.
PubMed: 14694551
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
Compounding variants rescue the effect of a deleterious ADAMTS13 mutation in a child with severe congenital heart disease
Authors: Katneni UK, Hunt R, Hettiarachchi GK, Hamasaki-Katagiri N, Kimchi-Sarfaty C, Ibla JC.
Source: Thromb Res (2017)
Citation: Thromb Res. 2017 Oct;158:98-101. doi: 10.1016/j.thromres.2017.08.016. Epub 2017 Aug 24.
PubMed: 28866379 · DOI: 10.1016/j.thromres.2017.08.016

Amino-acid property change

Residue substitution
I → F at 673
AlphaMissense score
0.7007
Likely pathogenic
CSV class: LPath
Hydrophobicity
hydrophobic → hydrophobic (unchanged)
Charge
neutral → neutral (unchanged)
Polarity
nonpolar → nonpolar (unchanged)
Size
large → large (unchanged)
Residue type
aliphatic → aromatic
Typical protein position
buried → buried (unchanged)
Hydropathy index
4.5 → 2.8
Molecular weight
131.2 → 165.2
Original residue details
I · isoleucine
code: Ile
hydro: hydrophobic
charge: neutral
polarity: nonpolar
size: large
type: aliphatic
Variant residue details
F · phenylalanine
code: Phe
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 673 highlighted in red.
AlphaFold Q76LX8 ADAMTS13 structure
Domain: Spacer
Domain colours match the homepage domain viewer.

Patient summary

Countries represented
Japan (6); Switzerland (1)
Phenotype
cTTP (7)
Zygosity
compound_heterozygous (7)
Sex
female (5); male (2)
Pregnancy-related
unknown (3); no (3); yes (1)
Triggers
unknown (4); none (2); pregnancy (1)
Treatment
unknown (4); PI (2); TAK (1)
ADAMTS13 activity
n=7; median=0.5; range=0.5–3.9
Age of onset
n=4; median=11.5; range=3–26
Age of diagnosis
n=1; median=27; range=27–27
Platelet count
n=4; median=40.5; range=22–89

Variant fields

mut_syn_HGVS
c.2017A>T
cdna_numb_HGVS
2017
cdna_numb_legacy
2017
nt_change
A>T
n_bp
1
nuc_numb
2017
g_numb
g16
aa_numb_HGVS
673
aa_numb_legacy
673
aa_first
Ile
aa_last
Phe
aa_syn
p.Ile673Phe
codon_first
ATC
codon_last
TTC
gnomAD_AC
11
gnomAD_AN
1613856
gnomAD_AF
0.00000681
g_id
g16
g_name
ADAMTS13
comments
Likely pathogenic
refState
complete
ref_id
21, 71, 72, 179, 205, 214, 226, 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
140 332 230 214 cTTP compound_heterozygous Japan female <3 unknown <0.5 89 unknown unknown unknown
141 332 345 214 cTTP compound_heterozygous Japan male <4 unknown <0.5 41 unknown unknown unknown
156 332 231 214 cTTP compound_heterozygous Japan female <19 unknown <0.5 22 unknown unknown unknown
163 332 231 226 cTTP compound_heterozygous Japan female unknown unknown <0.5 unknown no unknown unknown
219 332 133 21 cTTP compound_heterozygous Switzerland female 26 27 3.9 40 yes pregnancy TAK
270 332 230 179 cTTP compound_heterozygous Japan female unknown unknown <3 unknown no none PI
271 332 345 179 cTTP compound_heterozygous Japan male unknown unknown <3 unknown no none PI