UniProtKB/Swiss-Prot P07949: Variant p.Gly691Ser

Proto-oncogene tyrosine-protein kinase receptor Ret
Gene: RET
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Variant information Variant position:

691 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 Glycine (G) to Serine (S) at position 691 (G691S, p.Gly691Ser). 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 glycine (G) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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
Polymorphism:

The Cys-982 polymorphism may be associated with an increased risk for developing Hirschsprung disease. Additional information on the polymorphism described.
Other resources:

Links to websites of interest for the variant.

Variant rs1799939 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

1114 The length of the canonical sequence.
Location on the sequence:

SAEMTFRRPAQAFPVSYSSS G ARRPSLDSMENQVSVDAFKI 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                         SAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKI

Mouse                         SAEMTFCRPAQGFPISYSSSGTRRPSLDSTENQVPVDSFKI

Rat                           SAEMTFCRPAQGFPISYSSSGTRRPSLDSMENQVSVDSFKI

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	29 – 1114	Proto-oncogene tyrosine-protein kinase receptor Ret
Chain	29 – 707	Extracellular cell-membrane anchored RET cadherin 120 kDa fragment
Topological domain	658 – 1114	Cytoplasmic
Modified residue	696 – 696	Phosphoserine
Glycosylation	688 – 688	O-linked (GlcNAc) serine
Mutagenesis	707 – 707	D -> N. Impaired cleavage by caspase-3 and loss of induced cell death.

Literature citations
Novel germline RET proto-oncogene mutations associated with medullary thyroid carcinoma (MTC): mutation analysis in Japanese patients with MTC.
Kitamura Y.; Goodfellow P.J.; Shimizu K.; Nagahama M.; Ito K.; Kitagawa W.; Akasu H.; Takami H.; Tanaka S.; Wells S.A. Jr.;
Oncogene 14:3103-3106(1997)
Cited for: VARIANTS MTC; MEN2A AND MEN2B; VARIANT SER-691; Mutations of the RET-GDNF signaling pathway in Ondine's curse.
Amiel J.; Salomon R.; Attie T.; Pelet A.; Trang H.; Mokhtari M.; Gaultier C.; Munnich A.; Lyonnet S.;
Am. J. Hum. Genet. 62:715-717(1998)
Cited for: VARIANT HSCR1 LEU-1039; VARIANT SER-691; Molecular analysis of congenital central hypoventilation syndrome.
Sasaki A.; Kanai M.; Kijima K.; Akaba K.; Hashimoto M.; Hasegawa H.; Otaki S.; Koizumi T.; Kusuda S.; Ogawa Y.; Tuchiya K.; Yamamoto W.; Nakamura T.; Hayasaka K.;
Hum. Genet. 114:22-26(2003)
Cited for: VARIANTS HIS-67; HIS-114; GLU-432; ASN-489; SER-691 AND CYS-982; 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] GLN-163; ASN-278; MET-292; ASN-489; SER-691; THR-749; SER-826; LEU-844; CYS-982 AND TYR-1112;

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.