UniProtKB/SwissProt variant VAR

Variant information

Variant position:

634

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:

LP/P [Disclaimer]

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 Cysteine (C) to Arginine (R) at position 634 (C634R, p.Cys634Arg).

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 (C) to large size and basic (R)

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 MEN2A, pheochromocytoma and MTC; familial form; also found as somatic mutation in a sporadic thyroid carcinoma.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs75076352 [ dbSNP | Ensembl ]

Sequence information

Variant position:

634

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:

EEEKCFCEPEDIQDPLCDEL C RTVIAAAVLFSFIVSVLLSA

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                         EEEKCFCEPEDIQDPLCDELCRTVIAAAVLFSFIVSVLLSA

Mouse                         DEKKCFCEPEDSQGPLCDALCRTIITAA-LFSLIISILLSI

Rat                           DEKKCFCEPEDSQGPLCDELCRTVITAAVLFSFIISVLLST

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	29 – 635	Extracellular

Literature citations

Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC.
Donis-Keller H.; Dou S.; Chi D.; Carlson K.M.; Toshima K.; Lairmore T.C.; Howe J.R.; Moley J.F.; Goodfellow P.; Wells S.A. Jr.;
Hum. Mol. Genet. 2:851-856(1993)
Cited for: VARIANTS MEN2A/MTC TRP-611; SER-618; ARG-620; TYR-620 AND ARG-634;

Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A.
Mulligan L.M.; Kwok J.B.J.; Healey C.S.; Elsdon M.J.; Eng C.; Gardner E.; Love D.R.; Mole S.E.; Moore J.K.; Papi L.; Ponder M.A.; Telenius H.; Tunnacliffe A.; Ponder B.A.J.;
Nature 363:458-460(1993)
Cited for: VARIANTS MEN2A GLY-618; 632-ASP--ARG-634; GLY-634; PHE-634; TYR-634 AND SER-634;

Germline mutations of the RET proto-oncogene in eight Japanese patients with multiple endocrine neoplasia type 2A (MEN2A).
Takiguchi-Shirahama S.; Koyama K.; Miyauchi A.; Wakasugi T.; Oishi S.; Takami H.; Hikiji K.; Nakamura Y.;
Hum. Genet. 95:187-190(1995)
Cited for: VARIANTS MEN2A SER-618; SER-620; ARG-634 AND TYR-634;

Germ-line mutations in nonsyndromic pheochromocytoma.
Neumann H.P.H.; Bausch B.; McWhinney S.R.; Bender B.U.; Gimm O.; Franke G.; Schipper J.; Klisch J.; Altehoefer C.; Zerres K.; Januszewicz A.; Smith W.M.; Munk R.; Manz T.; Glaesker S.; Apel T.W.; Treier M.; Reineke M.; Walz M.K.; Hoang-Vu C.; Brauckhoff M.; Klein-Franke A.; Klose P.; Schmidt H.; Maier-Woelfle M.; Peczkowska M.; Szmigielski C.; Eng C.;
N. Engl. J. Med. 346:1459-1466(2002)
Cited for: VARIANTS PHEOCHROMOCYTOMA ARG-634; GLY-634; TYR-634; SER-634; PHE-634; TRP-634 AND PHE-791;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P07949: Variant p.Cys634Arg