UniProtKB/Swiss-Prot P04629: Variant p.His604Tyr

High affinity nerve growth factor receptor
Gene: NTRK1
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Variant information Variant position:

604 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 Histidine (H) to Tyrosine (Y) at position 604 (H604Y, p.His604Tyr). 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 polar (H) to large size and aromatic (Y) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

2 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
Other resources:

Links to websites of interest for the variant.

Variant rs6336 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

PLLMVFEYMRHGDLNRFLRS H GPDAKLLAGGEDVAPGPLGL 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                         PLLMVFEYMRHGDLNRFLRSHGPDAKLLAGGEDVAPGPLGL

Mouse                         PLLMVFEYMRHGDLNRFLRSHGPDAKLLAGGEDVAPGPLGL

Rat                           PLLMVFEYMRHGDLNRFLRSHGPDAKLLAGGEDVAPGPLGL

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	33 – 796	High affinity nerve growth factor receptor
Topological domain	440 – 796	Cytoplasmic
Domain	510 – 781	Protein kinase

Literature citations
Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor.
Mardy S.; Miura Y.; Endo F.; Matsuda I.; Sztriha L.; Frossard P.; Moosa A.; Ismail E.A.R.; Macaya A.; Andria G.; Toscano E.; Gibson W.; Graham G.E.; Indo Y.;
Am. J. Hum. Genet. 64:1570-1579(1999)
Cited for: VARIANTS CIPA PRO-213; TRP-649 AND SER-714; VARIANTS SER-85; TYR-604 AND VAL-613; Mutation analysis reveals novel sequence variants in NTRK1 in sporadic human medullary thyroid carcinoma.
Gimm O.; Greco A.; Hoang-Vu C.; Dralle H.; Pierotti M.A.; Eng C.;
J. Clin. Endocrinol. Metab. 84:2784-2787(1999)
Cited for: VARIANTS TYR-604; VAL-613 AND GLN-780; Characterization of single-nucleotide polymorphisms in coding regions of human genes.
Cargill M.; Altshuler D.; Ireland J.; Sklar P.; Ardlie K.; Patil N.; Shaw N.; Lane C.R.; Lim E.P.; Kalyanaraman N.; Nemesh J.; Ziaugra L.; Friedland L.; Rolfe A.; Warrington J.; Lipshutz R.; Daley G.Q.; Lander E.S.;
Nat. Genet. 22:231-238(1999)
Cited for: VARIANTS TYR-604 AND VAL-613; A novel TRK A (NTRK1) mutation associated with hereditary sensory and autonomic neuropathy type V.
Houlden H.; King R.H.; Hashemi-Nejad A.; Wood N.W.; Mathias C.J.; Reilly M.; Thomas P.K.;
Ann. Neurol. 49:521-525(2001)
Cited for: VARIANT CIPA CYS-359; VARIANTS TYR-604 AND VAL-613; Congenital insensitivity to pain with anhidrosis (CIPA): effect of TRKA (NTRK1) missense mutations on autophosphorylation of the receptor tyrosine kinase for nerve growth factor.
Mardy S.; Miura Y.; Endo F.; Matsuda I.; Indo Y.;
Hum. Mol. Genet. 10:179-188(2001)
Cited for: CHARACTERIZATION OF VARIANTS CIPA PRO-93; PRO-213; ARG-522; ARG-577; TRP-649; CYS-654 AND SER-714; CHARACTERIZATION OF VARIANTS SER-85; TYR-604; VAL-613 AND TYR-674; Patterns of somatic mutation in human cancer genomes.
Greenman C.; Stephens P.; Smith R.; Dalgliesh G.L.; Hunter C.; Bignell G.; Davies H.; Teague J.; Butler A.; Stevens C.; Edkins S.; O'Meara S.; Vastrik I.; Schmidt E.E.; Avis T.; Barthorpe S.; Bhamra G.; Buck G.; Choudhury B.; Clements J.; Cole J.; Dicks E.; Forbes S.; Gray K.; Halliday K.; Harrison R.; Hills K.; Hinton J.; Jenkinson A.; Jones D.; Menzies A.; Mironenko T.; Perry J.; Raine K.; Richardson D.; Shepherd R.; Small A.; Tofts C.; Varian J.; Webb T.; West S.; Widaa S.; Yates A.; Cahill D.P.; Louis D.N.; Goldstraw P.; Nicholson A.G.; Brasseur F.; Looijenga L.; Weber B.L.; Chiew Y.-E.; DeFazio A.; Greaves M.F.; Green A.R.; Campbell P.; Birney E.; Easton D.F.; Chenevix-Trench G.; Tan M.-H.; Khoo S.K.; Teh B.T.; Yuen S.T.; Leung S.Y.; Wooster R.; Futreal P.A.; Stratton M.R.;
Nature 446:153-158(2007)
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ARG-80; VAL-107; MET-237; GLY-238; GLY-260; GLN-444; CYS-452; THR-566; TYR-604; VAL-613; GLN-780 AND ILE-790;

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.