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UniProtKB/Swiss-Prot P40692: Variant p.Pro603Arg

DNA mismatch repair protein Mlh1
Gene: MLH1
Variant information

Variant position:  603
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  US
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 Proline (P) to Arginine (R) at position 603 (P603R, p.Pro603Arg).
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 hydrophobic (P) to large size and basic (R)
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

Variant description:  In HNPCC2; unknown pathological significance; no effect on MLH1 splicing.
Any additional useful information about the variant.

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



Sequence information

Variant position:  603
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  756
The length of the canonical sequence.

Location on the sequence:   FDLAMLALDSPESGWTEEDG  P KEGLAEYIVEFLKKKAEMLA
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                         FDLAMLALDSPESGWTEEDGPKEGLAEYIVEFLKKKAEMLA

Mouse                         FDLAMLALDSPESGWTEDDGPKEGLAEYIVEFLKKKAEMLA

Rat                           FDFAMLALDSPESGWTEEDGPKEGLAEYIVEFLKKKAKMLA

Slime mold                    YSLLLVSLDSPLSGWMESDGPKDKIADYLTKLLISKKELLN

Baker's yeast                 DDIVLYNLLSEFDE-LNDDASKEK----IISKIWDMSSMLN

Fission yeast                 SDLFEIV-----NG-DEDKSESEK----FTRLLVSRRDMLK

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 2 – 756 DNA mismatch repair protein Mlh1
Region 410 – 650 Interaction with EXO1


Literature citations

Sixteen rare sequence variants of the hMLH1 and hMSH2 genes found in a cohort of 254 suspected HNPCC (hereditary non-polyposis colorectal cancer) patients: mutations or polymorphisms?
Mueller-Koch Y.; Kopp R.; Lohse P.; Baretton G.; Stoetzer A.; Aust D.; Daum J.; Kerker B.; Gross M.; Dietmeier W.; Holinski-Feder E.;
Eur. J. Med. Res. 6:473-482(2001)
Cited for: VARIANTS HNPCC2 VAL-80; PRO-329; ARG-603; ALA-618; LEU-648 AND PRO-662; VARIANT HNPCC ARG-689;

hMLH1 and hMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancer.
Rossi B.M.; Lopes A.; Oliveira Ferreira F.; Nakagawa W.T.; Napoli Ferreira C.C.; Casali Da Rocha J.C.; Simpson C.C.; Simpson A.J.G.;
Ann. Surg. Oncol. 9:555-561(2002)
Cited for: VARIANTS HNPCC2 SER-338; ARG-603; THR-618 AND TYR-718;

A large fraction of unclassified variants of the mismatch repair genes MLH1 and MSH2 is associated with splicing defects.
Tournier I.; Vezain M.; Martins A.; Charbonnier F.; Baert-Desurmont S.; Olschwang S.; Wang Q.; Buisine M.P.; Soret J.; Tazi J.; Frebourg T.; Tosi M.;
Hum. Mutat. 29:1412-1424(2008)
Cited for: VARIANT HNPCC2 ILE-330 DEL; VARIANTS HIS-41; ARG-67; ARG-77; SER-98; SER-101; ASP-101; LYS-116; MET-117; ASN-126; MET-213; SER-215; SER-216; PHE-260; CYS-265; HIS-265; ASP-320; ALA-326; ILE-330 DEL; TRP-474; GLN-474; ASP-539; PRO-549; THR-551; ARG-585; ARG-603; HIS-607; PRO-619; SER-640; LEU-640; VAL-655; SER-656; ARG-666; THR-681 AND ARG-689;

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.