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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P43246: Variant p.Gly674Arg

DNA mismatch repair protein Msh2
Gene: MSH2
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Variant information Variant position: help 674 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Glycine (G) to Arginine (R) at position 674 (G674R, p.Gly674Arg). 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: help Change from glycine (G) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In LYNCH1; decreased mismatch repair activity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 674 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 934 The length of the canonical sequence.
Location on the sequence: help DVYFEKDKQMFHIITGPNMG G KSTYIRQTGVIVLMAQIGCF 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         DVYFEKDKQMFHIITGPNMGGKSTYIRQTGVIVLMAQIGCF

Mouse                         DVHFEKDKQMFHIITGPNMGGKSTYIRQTGVIVLMAQIGCF

Rat                           DVHFEKDKQMFHIITGPNMGGKSTYIRQTGVIVLMAQIGCF

Bovine                        DVHFEKDKQMFHIITGPNMGGKSTYIRQTGVVVLMAQIGCF

Drosophila                    SVDFKKEECNMFIITGPNMGGKSTYIRSVGTAVLMAHIGAF

Slime mold                    DIDLTRGQSQFQIITGPNMGGKSTFIRQVGLIVLMAQIGCF

Baker's yeast                 DVTLESGKGDFLIITGPNMGGKSTYIRQVGVISLMAQIGCF

Fission yeast                 DVNLEHGSSELLIITGPNMGGKSTYIRQVGVITVMAQIGCP
Sequence annotation in neighborhood: help 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 – 934 DNA mismatch repair protein Msh2
Binding site 669 – 676
Mutagenesis 675 – 675 K -> R. No effect on mismatch binding, complete loss of DNA repair function when associated with MSH6 mutant R-1140.
Beta strand 671 – 674



Literature citations
A high incidence of MSH6 mutations in Amsterdam criteria II-negative families tested in a diagnostic setting.
Ramsoekh D.; Wagner A.; van Leerdam M.E.; Dinjens W.N.; Steyerberg E.W.; Halley D.J.; Kuipers E.J.; Dooijes D.;
Gut 57:1539-1544(2008)
Cited for: VARIANT LYNCH1 ARG-674; Functional analysis of HNPCC-related missense mutations in MSH2.
Lutzen A.; de Wind N.; Georgijevic D.; Nielsen F.C.; Rasmussen L.J.;
Mutat. Res. 645:44-55(2008)
Cited for: CHARACTERIZATION OF VARIANTS LYNCH1 HIS-167; THR-305: LEU-622; ARG-639; ARG-674; PHE-697 AND THR-834; A rapid and cell-free assay to test the activity of lynch syndrome-associated MSH2 and MSH6 missense variants.
Drost M.; Zonneveld J.B.; van Hees S.; Rasmussen L.J.; Hofstra R.M.; de Wind N.;
Hum. Mutat. 33:488-494(2012)
Cited for: CHARACTERIZATION OF VARIANTS LYNCH1 MET-44; VAL-45; HIS-167; THR-305; PHE-390; ASN-596 DEL; ARG-639; ARG-674; PHE-697; PHE-723 AND GLY-886; CHARACTERIZATION OF VARIANTS ASP-165; HIS-177; VAL-272; LEU-385; LEU-519; ALA-675; GLU-759; VAL-805; GLY-843 AND LEU-860;
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.