Home  |  Contact

UniProtKB/Swiss-Prot P40692: Variant p.Gly67Trp

DNA mismatch repair protein Mlh1
Gene: MLH1
Variant information

Variant position:  67
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 Glycine (G) to Tryptophan (W) at position 67 (G67W, p.Gly67Trp).
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 large size and aromatic (W)
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.
Any additional useful information about the variant.

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



Sequence information

Variant position:  67
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:   IQVIVKEGGLKLIQIQDNGT  G IRKEDLDIVCERFTTSKLQS
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                         IQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQS

Mouse                         IQVVVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQT

Rat                           IQVIVREGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQT

Slime mold                    ITVTVKDGGMKFLQIQDNGSGIRLEDMGIVCERFTTSKLTK

Baker's yeast                 IDILVKEGGIKVLQITDNGSGINKADLPILCERFTTSKLQK

Fission yeast                 IDVLLKDGGLKLLQITDNGSGIQYDDLPYLCQRFSTSKIDN

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
Binding site 63 – 63 ATP
Alternative sequence 1 – 241 Missing. In isoform 2.
Alternative sequence 1 – 101 MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRG -> MAF. In isoform 3.


Literature citations

Neurofibromatosis and early onset of cancers in hMLH1-deficient children.
Wang Q.; Lasset C.; Desseigne F.; Frappaz D.; Bergeron C.; Navarro C.; Ruano E.; Puisieux A.;
Cancer Res. 59:294-297(1999)
Cited for: VARIANT HNPCC2 TRP-67;

Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in 75 French kindreds with nonpolyposis colorectal cancer.
Wang Q.; Lasset C.; Desseigne F.; Saurin J.-C.; Maugard C.; Navarro C.; Ruano E.; Descos L.; Trillet-Lenoir V.; Bosset J.-F.; Puisieux A.;
Hum. Genet. 105:79-85(1999)
Cited for: VARIANTS HNPCC2 TRP-67; MET-117; GLY-182 AND LYS-616 DEL; VARIANT HNPCC TRP-755;

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.