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UniProtKB/Swiss-Prot P07949: Variant p.Cys620Arg

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

Variant position:  620
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 620 (C620R, p.Cys620Arg).
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; familial and sporadic forms.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  620
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:   RGIKAGYGTCNCFPEEEKCF  C EPEDIQDPLCDELCRTVIAA
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                         RGIKAGYGTCNCFPEEEKCFCEPEDIQDPLCDELCRTVIAA

Mouse                         QGIKAGYGICNCFPDEKKCFCEPEDSQGPLCDALCRTIITA

Rat                           QGIKAGYGICNCFPDEKKCFCEPEDSQGPLCDELCRTVITA

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.

TypePositionsDescription
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;

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;

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;

Mutation analysis of the RET receptor tyrosine kinase in Hirschsprung disease.
Angrist M.; Bolk S.; Thiel B.; Puffenberger E.G.; Hofstra R.M.W.; Buys C.H.C.M.; Cass D.T.; Chakravarti A.;
Hum. Mol. Genet. 4:821-830(1995)
Cited for: VARIANTS HSCR1 LEU-20; SER-93; GLN-330; TYR-609 AND ARG-620; VARIANT CYS-982;

Mutations in three genes are found associated with the development of Hirschsprung disease: RET, EDNRB and EDN3.
Hofstra R.M.W.; Osinga J.; Stulp R.P.; Scheffer H.; Meijers C.; Buys C.H.C.M.;
Cited for: VARIANTS HSCR1 TYR-157; LYS-359; TYR-609; ARG-620; ASN-1059 DEL AND PRO-1061;

Frequency of RET mutations in long- and short-segment Hirschsprung disease.
Seri M.; Yin L.; Barone V.; Bolino A.; Celli I.; Bocciardi R.; Pasini B.; Ceccherini I.; Lerone M.; Kristoffersson U.; Larsson L.T.; Casasa J.M.; Cass D.T.; Abramowicz M.J.; Vanderwinden J.-M.; Kravcenkiene I.; Baric I.; Silengo M.; Martucciello G.; Romeo G.;
Hum. Mutat. 9:243-249(1997)
Cited for: VARIANTS HSCR1 PRO-180; GLN-313; ARG-620 AND PHE-791;

Hirschsprung disease in MEN 2A: increased spectrum of RET exon 10 genotypes and strong genotype-phenotype correlation.
Decker R.A.; Peacock M.L.; Watson P.;
Hum. Mol. Genet. 7:129-134(1998)
Cited for: VARIANTS MEN2A TYR-609; SER-618; ARG-620 AND TRP-620; VARIANTS HSCR1 TYR-609; SER-618; ARG-620 AND TRP-620;

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.