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UniProtKB/Swiss-Prot P43246: Variant p.Ile145Met

DNA mismatch repair protein Msh2
Gene: MSH2
Variant information

Variant position:  145
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Isoleucine (I) to Methionine (M) at position 145 (I145M, p.Ile145Met).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
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 HNPCC1; unknown pathological significance; normal mismatch repair activity.
Any additional useful information about the variant.

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

Sequence information

Variant position:  145
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  934
The length of the canonical sequence.

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.


Mouse                         PGNLSQFEDILFGNN--------DMSASVGVMGIKMAVV-D

Rat                           PGNLSQFEDILFGNN--------DMATSIGIMGIKLSTV-D

Bovine                        PGNLSQFEDILFGNN--------DMSASIGVVGVKMSTV-D

Drosophila                    PGNLLQFEDILFSNK--------EVLVGNSIISLLVKLDGG

Slime mold                    PGNTQMFEDVLLNGN----------CEGSVMMALKVTRE-K

Baker's yeast                 PGNIEQVNELMNMNI--------DSSIIIASLKVQWNSQ-D


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.

Chain 2 – 934 DNA mismatch repair protein Msh2

Literature citations

Verification of the three-step model in assessing the pathogenicity of mismatch repair gene variants.
Kansikas M.; Kariola R.; Nystroem M.;
Hum. Mutat. 32:107-115(2011)
Cited for: CHARACTERIZATION OF VARIANTS HNPCC1 PRO-33; MET-44; VAL-45; SER-127; MET-145; ASP-161; ARG-162; ARG-164; PRO-173; ARG-187; PRO-187; VAL-272; TYR-333; LEU-519; ASN-603; PRO-636; ALA-674; VAL-688; PHE-697; 745-ILE-ILE-746 DEL; LYS-749; THR-834; GLY-886 AND GLU-923; CHARACTERIZATION OF VARIANTS ASP-322 AND ILE-722; FUNCTION;

Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study).
Kurzawski G.; Suchy J.; Lener M.; Klujszo-Grabowska E.; Kladny J.; Safranow K.; Jakubowska K.; Jakubowska A.; Huzarski T.; Byrski T.; Debniak T.; Cybulski C.; Gronwald J.; Oszurek O.; Oszutowska D.; Kowalska E.; Gozdz S.; Niepsuj S.; Slomski R.; Plawski A.; Lacka-Wojciechowska A.; Rozmiarek A.; Fiszer-Maliszewska L.; Bebenek M.; Sorokin D.; Sasiadek M.M.; Stembalska A.; Grzebieniak Z.; Kilar E.; Stawicka M.; Godlewski D.; Richter P.; Brozek I.; Wysocka B.; Limon J.; Jawien A.; Banaszkiewicz Z.; Janiszewska H.; Kowalczyk J.; Czudowska D.; Scott R.J.; Lubinski J.;
Clin. Genet. 69:40-47(2006)
Cited for: VARIANTS HNPCC1 THR-2; LEU-92 DEL; MET-145; PHE-390 AND ALA-853; VARIANT ASP-322;

Mismatch repair analysis of inherited MSH2 and/or MSH6 variation pairs found in cancer patients.
Kantelinen J.; Kansikas M.; Candelin S.; Hampel H.; Smith B.; Holm L.; Kariola R.; Nystrom M.;
Hum. Mutat. 33:1294-1301(2012)
Cited for: CHARACTERIZATION OF VARIANTS SER-127; MET-145; GLN-205; ASP-322; PRO-328; ILE-367; GLU-487 AND ILE-909;

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.