Variant detail

mut_id 117 · c.2746C>T · p.Arg916Cys

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Evidence at a glance

4
Linked patients
4
Patient-variant records
6
Linked references
3
Countries reported
cTTP (4)
Common phenotype
compound_heterozygous (3)
Common zygosity

Summary

Point missense_variant Conflicting classifications of pathogenicity Residue 916 AlphaMissense key R916C
HGVS
c.2746C>T
Protein change
p.Arg916Cys
rsID
rs374444423
ClinVar ID
1303178
GRCh38 coordinate
133448613
Location
exon 22
gnomAD AF
3.17E-05
Domain
TSP type-1 5
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
A successfully treated case of an acute presentation of congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome) with decreased ADAMTS13 during late stage of pregnancy
Authors: Nonaka T, Yamaguchi M, Nishijima K, Moriyama M, Takakuwa K, Enomoto T.
Source: J Obstet Gynaecol Res (2021)
Citation: J Obstet Gynaecol Res. 2021 May;47(5):1892-1897. doi: 10.1111/jog.14737. Epub 2021 Mar 9.
PubMed: 33751717 · DOI: 10.1111/jog.14737
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
Inherited thrombotic thrombocytopenic purpura mimicking immune thrombocytopenic purpura during pregnancy: a case report
Authors: Romão de Souza V Jr, Beatriz Cavalcante de Oliveira A, Maria Vanderlei A, Queiroz da Mota Silveira Aroucha A, Pontes Duarte B, Nunes Machado A, Netto Chaer L, Wanderley de Barros Correia C, da Conceição de Barros Correia M, Freire Hazin Costa M.
Source: J Med Case Rep (2018)
Citation: J Med Case Rep. 2018 Jan 22;12(1):15. doi: 10.1186/s13256-017-1545-3.
PubMed: 29357939 · DOI: 10.1186/s13256-017-1545-3
Multiple in silico tools predict phenotypic manifestations in congenital thrombotic thrombocytopenic purpura
Authors: Hing ZA, Schiller T, Wu A, Hamasaki-Katagiri N, Struble EB, Russek-Cohen E, Kimchi-Sarfaty C.
Source: Br J Haematol (2013)
Citation: Br J Haematol. 2013 Mar;160(6):825-37. doi: 10.1111/bjh.12214. Epub 2013 Jan 24.
PubMed: 23346910 · DOI: 10.1111/bjh.12214

Amino-acid property change

Residue substitution
R → C at 916
AlphaMissense score
0.1720
Likely benign
CSV class: LBen
Hydrophobicity
hydrophilic → hydrophilic (unchanged)
Charge
postive → neutral
Polarity
polar → polar (unchanged)
Size
large → medium
Residue type
basic → Unknown
Typical protein position
surface → buried
Hydropathy index
-4.5 → 2.5
Molecular weight
174.2 → 121.2
Original residue details
R · arginine
code: Arg
hydro: hydrophilic
charge: postive
polarity: polar
size: large
type: basic
Variant residue details
C · cysteine
code: Cys
hydro: hydrophilic
charge: neutral
polarity: polar
size: medium
type:

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 916 highlighted in red.
AlphaFold Q76LX8 ADAMTS13 structure
Domain: TSP type-1 5
Domain colours match the homepage domain viewer.

Patient summary

Countries represented
USA (2); Armenia (1); France (1)
Phenotype
cTTP (4)
Zygosity
compound_heterozygous (3); homozygous (1)
Sex
female (3); unknown (1)
Pregnancy-related
yes (2); no (1); unknown (1)
Triggers
pregnancy (2); infection (1); unknown (1)
Treatment
unknown (2); on-demand PI (1); on demand PI (1)
ADAMTS13 activity
n=4; median=5; range=3–9
Age of onset
n=3; median=32; range=21–43
Age of diagnosis
n=3; median=43; range=21–48
Platelet count
n=3; median=14; range=9–60

Variant fields

mut_syn_HGVS
c.2746C>T
cdna_numb_HGVS
2746
cdna_numb_legacy
2746
nt_change
C>T
n_bp
1
nuc_numb
2746
g_numb
g16
aa_numb_HGVS
916
aa_numb_legacy
916
aa_first
Arg
aa_last
Cys
aa_syn
p.Arg916Cys
codon_first
CGT
codon_last
TGT
coordinate_GRCh38
133448613
gnomAD_AC
51
gnomAD_AN
1610268
gnomAD_AF
3.17E-05
clinvar_id
1303178
clinvar_classification
Conflicting classifications of pathogenicity
g_id
g16
g_name
ADAMTS13
comments
Pathogenic
refState
complete
ref_id
7, 12, 43, 72, 84, 131, 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
14 117 104 43 cTTP homozygous Armenia unknown 43 43 <3 14 no infection on-demand PI
64 117 273 84 cTTP compound_heterozygous USA female 32 48 <5 60 unknown unknown unknown
111 117 333 131 cTTP compound_heterozygous USA female 21 21 <5 9 yes pregnancy on demand PI
299 117 133 12 cTTP compound_heterozygous France female unknown unknown 9 unknown yes pregnancy unknown