Variant detail

mut_id 49 · c.1058C>T · p.Pro353Leu

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Evidence at a glance

6
Linked patients
6
Patient-variant records
9
Linked references
3
Countries reported
cTTP (6)
Common phenotype
compound_heterozygous (6)
Common zygosity

Summary

Point missense_variant Likely pathogenic Residue 353 AlphaMissense key P353L
HGVS
c.1058C>T
Protein change
p.Pro353Leu
rsID
rs281875338
ClinVar ID
68800
GRCh38 coordinate
133432658
Location
exon 9
gnomAD AF
2.82E-05
Domain
Disintegrin
Gene
ADAMTS13

External links

dbSNP ClinVar gnomAD

References

NEPHRO-ZEBRA-a neonate with severe jaundice, persistent thrombocytopenia & recurrent acute kidney injury later in childhood: Joining the dots!
Authors: Sethi SK, Yadav SP, Moideen A, Raina R.
Source: J Nephrol (2024)
Citation: J Nephrol. 2024 Apr;37(3):827-829. doi: 10.1007/s40620-023-01848-w. Epub 2024 Jan 25.
PubMed: 38267796 · DOI: 10.1007/s40620-023-01848-w
Congenital Thrombotic Thrombocytopenic Purpura: A Rare Cause of Recurrent Thrombocytopenia and Anemia
Authors: Assiri M, AlMalki A, AlHunif B, AlMofareh M.
Source: Cureus (2023)
Citation: Cureus. 2023 Sep 10;15(9):e44988. doi: 10.7759/cureus.44988. eCollection 2023 Sep.
PubMed: 37822445 · DOI: 10.7759/cureus.44988
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
Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13
Authors: Pimanda JE, Maekawa A, Wind T, Paxton J, Chesterman CN, Hogg PJ.
Source: Blood (2004)
Citation: Blood. 2004 Jan 15;103(2):627-9. doi: 10.1182/blood-2003-04-1346. Epub 2003 Sep 25.
PubMed: 14512317 · DOI: 10.1182/blood-2003-04-1346
Remission of thrombotic thrombocytopenic purpura in a patient with compound heterozygous deficiency of von Willebrand factor-cleaving protease by infusion of solvent/detergent plasma
Authors: Kentouche K, Budde U, Furlan M, Scharfe V, Schneppenheim R, Zintl F.
Source: Acta Paediatr (2002)
Citation: Acta Paediatr. 2002;91(10):1056-9. doi: 10.1080/080352502760311548.
PubMed: 12434890 · DOI: 10.1080/080352502760311548
ADAMTS genes and the risk of cerebral aneurysm
Authors: Arning A, Jeibmann A, Köhnemann S, Brokinkel B, Ewelt C, Berger K, Wellmann J, Nowak-Göttl U, Stummer W, Stoll M, Holling M.
Source: J Neurosurg (2016)
Citation: J Neurosurg. 2016 Aug;125(2):269-74. doi: 10.3171/2015.7.JNS154. Epub 2016 Jan 8.
PubMed: 26745484 · DOI: 10.3171/2015.7.JNS154
Novel homozygous ADAMTS13 mutation with neonatal presentation of congenital thrombotic thrombocytopenic purpura in two Indian origin babies
Authors: Debaditya Das, Ming Wei Lee, Shivani Dogra, Bikramjit Das, Joyce Lam, Sudip Sengupta, Rajat Bhattacharyya
Source: Pediatric Hematology Oncology Journal (2019)
Citation: Pediatric Hematology Oncology Journal, Valume 4, Issue 1, 2019. Pages 27-29, ISSN 2468-1245
DOI: 10.1016/j.phoj.2018.12.001
Two cases of congenital thrombotic thrombocytopenicpurpura associated with pregnancy
Authors: Bai X*, Su J, Yu Z, Wang Z and Ruan C
Source: ISTH 2012 (2012)
Citation: ISTH 2012
PubMed: ISTH 2012

Amino-acid property change

Residue substitution
P → L at 353
AlphaMissense score
0.3164
Likely benign
CSV class: LBen
Hydrophobicity
hydrophobic → hydrophobic (unchanged)
Charge
neutral → neutral (unchanged)
Polarity
nonpolar → nonpolar (unchanged)
Size
medium → large
Residue type
Unknown → aliphatic
Typical protein position
surface → buried
Hydropathy index
-1.6 → 3.8
Molecular weight
115.1 → 131.2
Original residue details
P · proline
code: Pro
hydro: hydrophobic
charge: neutral
polarity: nonpolar
size: medium
type:
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 353 highlighted in red.
AlphaFold Q76LX8 ADAMTS13 structure
Domain: Disintegrin
Domain colours match the homepage domain viewer.

Patient summary

Countries represented
Germany (4); Australia (1); France (1)
Phenotype
cTTP (6)
Zygosity
compound_heterozygous (6)
Sex
female (3); unknown (2); male (1)
Pregnancy-related
unknown (3); no (2); yes (1)
Triggers
none (5); pregnancy (1)
Treatment
unknown (3); none (2); PI (1)
ADAMTS13 activity
n=4; median=2; range=1–6
Age of onset
n=5; median=2; range=1–30
Age of diagnosis
n=3; median=10; range=3–46
Platelet count
Not available

Variant fields

mut_syn_HGVS
c.1058C>T
cdna_numb_HGVS
1058
cdna_numb_legacy
1058
nt_change
C>T
n_bp
1
nuc_numb
1058
g_numb
g16
aa_numb_HGVS
353
aa_numb_legacy
353
aa_first
Pro
aa_last
Leu
aa_syn
p.Pro353Leu
codon_first
CCT
codon_last
CTT
coordinate_GRCh38
133432658
gnomAD_AC
44
gnomAD_AN
1559872
gnomAD_AF
2.82E-05
clinvar_id
68800
clinvar_classification
Likely pathogenic
g_id
g16
g_name
ADAMTS13
comments
Pathogenic
refState
complete
ref_id
7, 12, 71, 72, 181, 186, 232, 305, 312, 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
167 49 133 232 cTTP compound_heterozygous Australia female 30 46 <1 unknown unknown none PI
246 49 347 305 cTTP compound_heterozygous Germany female 2 3 unknown unknown no none none
250 49 272 305 cTTP compound_heterozygous Germany male <1 10 <2 unknown no none none
298 49 133 12 cTTP compound_heterozygous France female unknown unknown 6 unknown yes pregnancy unknown
342 49 347 186 cTTP compound_heterozygous Germany unknown 2 unknown unknown unknown unknown none unknown
346 49 273 186 cTTP compound_heterozygous Germany unknown 4 unknown <2 unknown unknown none unknown