UniProtKB/Swiss-Prot P16234: Variant p.Asp842Val

Platelet-derived growth factor receptor alpha
Gene: PDGFRA
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Variant information Variant position:

842 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Aspartate (D) to Valine (V) at position 842 (D842V, p.Asp842Val). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Change from medium size and acidic (D) to medium size and hydrophobic (V) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

In a GIST sample; imatinib resistant, constitutively activated kinase. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121908585 [ dbSNP | Ensembl ]

Sequence information Variant position:

842 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1089 The length of the canonical sequence.
Location on the sequence:

RNVLLAQGKIVKICDFGLAR D IMHDSNYVSKGSTFLPVKWM The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         RNVLLAQGKIVKICDFGLARDIMHDSNYVSKGSTFLPVKWM

Mouse                         RNVLLAQGKIVKICDFGLARDIMHDSNYVSKGSTFLPVKWM

Rat                           RNVLLAQGKIVKICDFGLARDIMHDSNYVSKGSTFLPVKWM

Chicken                       RNVLLAQGKIVKICDFGLARDIMHDSNYVSKGSTFLPVKWM

Xenopus laevis                RNVLLAHGKIVKICDFGLARDIMHDSNYVSKGSTFLPVKWM

Zebrafish                     RNVLLSQGKIVKICDFGLARDIMHDNNYVSKGSTFLPVKWM

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	24 – 1089	Platelet-derived growth factor receptor alpha
Topological domain	550 – 1089	Cytoplasmic
Domain	593 – 954	Protein kinase
Modified residue	849 – 849	Phosphotyrosine; by autocatalysis
Alternative sequence	219 – 1089	Missing. In isoform 2.
Alternative sequence	744 – 1089	Missing. In isoform 3.

Literature citations
PDGFRA activating mutations in gastrointestinal stromal tumors.
Heinrich M.C.; Corless C.L.; Duensing A.; McGreevey L.; Chen C.J.; Joseph N.; Singer S.; Griffith D.J.; Haley A.; Town A.; Demetri G.D.; Fletcher C.D.; Fletcher J.A.;
Science 299:708-710(2003)
Cited for: FUNCTION IN PHOSPHORYLATION OF AKT1; MAP KINASES; STAT1 AND STAT3; INVOLVEMENT IN GIST; VARIANTS ASP-561; VAL-842; 842-ASP--HIS-845 DEL AND 845-HIS--PRO-448 DEL; CHARACTERIZATION OF VARIANTS ASP-561; VAL-842; 842-ASP--HIS-845 DEL AND 845-HIS--PRO-448 DEL; PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib.
Corless C.L.; Schroeder A.; Griffith D.; Town A.; McGreevey L.; Harrell P.; Shiraga S.; Bainbridge T.; Morich J.; Heinrich M.C.;
J. Clin. Oncol. 23:5357-5364(2005)
Cited for: INVOLVEMENT IN GIST; VARIANTS ASP-561; LYS-659; TYR-842; VAL-842; 842-ASP--HIS-845 DEL; 845-HIS--PRO-448 DEL AND CYS-849; CHARACTERIZATION OF VARIANTS ASP-561; LYS-659; TYR-842; VAL-842; 842-ASP--HIS-845 DEL; 845-HIS--PRO-448 DEL AND CYS-849; ACTIVITY REGULATION; The low frequency of clinical resistance to PDGFR inhibitors in myeloid neoplasms with abnormalities of PDGFRA might be related to the limited repertoire of possible PDGFRA kinase domain mutations in vitro.
von Bubnoff N.; Gorantla S.P.; Engh R.A.; Oliveira T.M.; Thone S.; Aberg E.; Peschel C.; Duyster J.;
Oncogene 30:933-943(2011)
Cited for: ROLE IN DISEASE; CHARACTERIZATION OF VARIANT VAL-842; ACTIVITY REGULATION;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.