UniProtKB/SwissProt variant VAR

Variant information

Variant position:

618

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 618 (C618R, p.Cys618Arg).

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, MTC and HSCR1.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs76262710 [ dbSNP | Ensembl ]

Sequence information

Variant position:

618

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:

EPRGIKAGYGTCNCFPEEEK C FCEPEDIQDPLCDELCRTVI

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                         EPRGIKAGYGTCNCFPEEEKCFCEPEDIQDPLCDELCRTVI

Mouse                         ERQGIKAGYGICNCFPDEKKCFCEPEDSQGPLCDALCRTII

Rat                           ERQGIKAGYGICNCFPDEKKCFCEPEDSQGPLCDELCRTVI

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

Germline RET mutations in MEN 2A and FMTC and their detection by simple DNA diagnostic tests.
Xue F.; Yu H.; Maurer L.H.; Memoli V.A.; Nutile-Mcmenemy N.; Schuster M.K.; Browden D.W.; Mao J.-I.; Noll W.W.;
Hum. Mol. Genet. 3:635-638(1994)
Cited for: VARIANTS MEN2A/MTC ARG-618; SER-618; PHE-620; ARG-620; PHE-634; GLY-634 AND TYR-634;

RET proto-oncogene mutations in inherited and sporadic medullary thyroid cancer.
Blaugrund J.E.; Johns M.M. Jr.; Eby Y.J.; Ball D.W.; Baylin S.B.; Hruban R.H.; Sidransky D.;
Hum. Mol. Genet. 3:1895-1897(1994)
Cited for: VARIANTS MTC/MEN2A TYR-609; ARG-618; SER-618 AND SER-620;

Diverse phenotypes associated with exon 10 mutations of the RET proto-oncogene.
Mulligan L.M.; Eng C.; Attie T.; Lyonnet S.; Marsh D.J.; Hyland V.J.; Robinson B.G.; Frilling A.; Verellen-Dumoulin C.; Safar A.; Venter D.J.; Munnich A.; Ponder B.A.J.;
Hum. Mol. Genet. 3:2163-2167(1994)
Cited for: VARIANTS HSCR1 TRP-609; ARG-618 AND ARG-620; VARIANT MEN2A ARG-618; VARIANT MTC ARG-620;

Cys 618 Arg mutation in the RET proto-oncogene associated with familial medullary thyroid carcinoma and maternally transmitted Hirschsprung's disease suggesting a role for imprinting.
Peretz H.; Luboshitsky R.; Baron E.; Biton A.; Gershoni R.; Usher S.; Grynberg E.; Yakobson E.; Graff E.; Lapidot M.;
Hum. Mutat. 10:155-159(1997)
Cited for: VARIANT MTC ARG-618; VARIANT HSCR1 ARG-618;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P07949: Variant p.Cys618Arg