Variant detail

mut_id 283 · c.649G>C · p.Asp217His

Back Advanced search Full table

Evidence at a glance

3
Linked patients
3
Patient-variant records
4
Linked references
1
Countries reported
cTTP (3)
Common phenotype
compound_heterozygous (2)
Common zygosity

Summary

Point missense_variant Uncertain significance Residue 217 AlphaMissense key D217H
HGVS
c.649G>C
Protein change
p.Asp217His
rsID
rs782305581
ClinVar ID
303567
GRCh38 coordinate
133426308
Location
exon 6
gnomAD AF
0.0000218
Domain
Metalloprotease
Gene
ADAMTS13

External links

dbSNP ClinVar gnomAD

References

Hypercoagulability and Inflammatory Markers in a Case of Congenital Thrombotic Thrombocytopenic Purpura Complicated by Fetal Demise
Authors: Skeith L, Hurd K, Chaturvedi S, Chow L, Nicholas J, Lee A, Young D, Goodyear D, Soucie J, Girard L, Dufour A, Agbani EO.
Source: J Clin Med (2022)
Citation: J Clin Med. 2022 Nov 30;11(23):7115. doi: 10.3390/jcm11237115.
PubMed: 36498688 · DOI: 10.3390/jcm11237115
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
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
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

Amino-acid property change

Residue substitution
D → H at 217
AlphaMissense score
0.5928
Likely pathogenic
CSV class: LPath
Hydrophobicity
hydrophilic → hydrophilic (unchanged)
Charge
negative → postive
Polarity
polar → polar (unchanged)
Size
medium → large
Residue type
acidic → aromatic/basic
Typical protein position
surface → surface (unchanged)
Hydropathy index
-3.5 → -3.2
Molecular weight
133.1 → 155.2
Original residue details
D · aspartic acid
code: Asp
hydro: hydrophilic
charge: negative
polarity: polar
size: medium
type: acidic
Variant residue details
H · histidine
code: His
hydro: hydrophilic
charge: postive
polarity: polar
size: large
type: aromatic/basic

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

Patient summary

Countries represented
UK (3)
Phenotype
cTTP (3)
Zygosity
compound_heterozygous (2); heterozygous (1)
Sex
female (3)
Pregnancy-related
yes (2); no (1)
Triggers
pregnancy (2); infection (1)
Treatment
PI (1); unknown (1); on-demand PI (1)
ADAMTS13 activity
n=2; median=13; range=5–21
Age of onset
n=1; median=2; range=2–2
Age of diagnosis
Not available
Platelet count
n=1; median=6; range=6–6

Variant fields

mut_syn_HGVS
c.649G>C
cdna_numb_HGVS
649
cdna_numb_legacy
649
nt_change
G>C
n_bp
1
nuc_numb
649
g_numb
g16
aa_numb_HGVS
217
aa_numb_legacy
217
aa_first
Asp
aa_last
His
aa_syn
p.Asp217His
codon_first
GAC
codon_last
CAC
coordinate_GRCh38
133426308
gnomAD_AC
35
gnomAD_AN
1605180
gnomAD_AF
0.0000218
clinvar_id
303567
clinvar_classification
Uncertain significance
g_id
g16
g_name
ADAMTS13
comments
Pathogenic
refState
complete
ref_id
23, 72, 138, 239, 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
5 283 . 23 cTTP heterozygous UK female unknown unknown 21 6 yes pregnancy PI
190 283 133 239 cTTP compound_heterozygous UK female unknown unknown unknown unknown yes pregnancy unknown
363 283 133 138 cTTP compound_heterozygous UK female 2 unknown <5 unknown no infection on-demand PI