Variant detail

mut_id 65 · c.1335delC · p.Phe445LeufsTer52

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Evidence at a glance

3
Linked patients
3
Patient-variant records
4
Linked references
1
Countries reported
cTTP (3)
Common phenotype
compound_heterozygous (3)
Common zygosity

Summary

Deletion frameshift_variant Residue 445 AlphaMissense key F445L
HGVS
c.1335delC
Protein change
p.Phe445LeufsTer52
GRCh38 coordinate
133436855
Location
exon 12
gnomAD AF
6.39E-07
Domain
Cysteine-rich
Gene
ADAMTS13

External links

gnomAD

References

Delayed diagnosis of congenital thrombotic thrombocytopenic purpura in a patient with recurrent strokes
Authors: Beltrami-Moreira M, DeSancho MT.
Source: J Thromb Thrombolysis (2022)
Citation: J Thromb Thrombolysis. 2022 Apr;53(3):734-738. doi: 10.1007/s11239-021-02629-7. Epub 2022 Jan 12.
PubMed: 35022991 · DOI: 10.1007/s11239-021-02629-7
Characterization and treatment of congenital thrombotic thrombocytopenic purpura
Authors: Alwan F, Vendramin C, Liesner R, Clark A, Lester W, Dutt T, Thomas W, Gooding R, Biss T, Watson HG, Cooper N, Rayment R, Cranfield T, van Veen JJ, Hill QA, Davis S, Motwani J, Bhatnagar N, Priddee N, David M, Crowley MP, Alamelu J, Lyall H, Westwood JP, Thomas M, Scully M.
Source: Blood (2019)
Citation: Blood. 2019 Apr 11;133(15):1644-1651. doi: 10.1182/blood-2018-11-884700. Epub 2019 Feb 15.
PubMed: 30770395 · DOI: 10.1182/blood-2018-11-884700
Reference 295
Upshaw-Schulman syndrome-associated ADAMTS13 variants possess proteolytic activity at the surface of endothelial cells and in simulated circulation
Authors: Letzer A, Lehmann K, Mess C, König G, Obser T, Peine S, Schneppenheim S, Budde U, Schneider SW, Schneppenheim R, Brehm MA
Source: PloS One (2020)
Citation: PLoS One. 2020 May 4;15(5):e0232637. doi: 10.1371/journal.pone.0232637.
PubMed: 32365113 · DOI: 10.1371/journal.pone.0232637

Amino-acid property change

Residue substitution
F → L at 445
AlphaMissense score
0.9876
Likely pathogenic
CSV class: LPath
Hydrophobicity
hydrophobic → hydrophobic (unchanged)
Charge
neutral → neutral (unchanged)
Polarity
nonpolar → nonpolar (unchanged)
Size
large → large (unchanged)
Residue type
aromatic → aliphatic
Typical protein position
buried → buried (unchanged)
Hydropathy index
2.8 → 3.8
Molecular weight
165.2 → 131.2
Original residue details
F · phenylalanine
code: Phe
hydro: hydrophobic
charge: neutral
polarity: nonpolar
size: large
type: aromatic
Variant residue details
L · leucine
code: Leu
hydro: hydrophobic
charge: neutral
polarity: nonpolar
size: large
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 445 highlighted in red.
AlphaFold Q76LX8 ADAMTS13 structure
Domain: Cysteine-rich
Domain colours match the homepage domain viewer.

Patient summary

Countries represented
China (3)
Phenotype
cTTP (3)
Zygosity
compound_heterozygous (3)
Sex
male (2); female (1)
Pregnancy-related
no (3)
Triggers
none (3)
Treatment
unknown (1); PI (1); nifedipine (1); dypyridamole (1); coated aldehyde oxystarch capsules (1)
ADAMTS13 activity
n=3; median=2.5; range=1–5
Age of onset
n=3; median=2; range=1–16
Age of diagnosis
n=3; median=10; range=4–21
Platelet count
n=2; median=55; range=34–76

Variant fields

mut_syn_HGVS
c.1335delC
cdna_numb_HGVS
1335
cdna_numb_legacy
1335
nt_change
Deletion
n_bp
1
nuc_numb
1335
g_numb
g16
aa_numb_HGVS
445
aa_numb_legacy
445
aa_first
Phe
aa_last
Leu
aa_syn
p.Phe445LeufsTer52
codon_first
TC
codon_last
T
coordinate_GRCh38
133436855
gnomAD_AC
1
gnomAD_AN
1564334
gnomAD_AF
6.39E-07
g_id
g16
g_name
ADAMTS13
comments
Pathogenic
refState
complete
ref_id
34, 73, 295, 304

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
256 65 29 304 cTTP compound_heterozygous China male <1 4 <5 unknown no none unknown
259 65 303 295 cTTP compound_heterozygous China male 16 21 <1 34 no none PI
308 65 98 34 cTTP compound_heterozygous China female 2 10 <2.5 76 no none nifedipine, dypyridamole, coated aldehyde oxystarch capsules