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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P40692: Variant p.Gly67Arg

DNA mismatch repair protein Mlh1
Gene: MLH1
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Variant information Variant position: help 67 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 67 (G67R, p.Gly67Arg). 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 LYNCH2; no effect on MLH1 splicing; decreased mismatch repair activity; loss of protein expression; loss of nuclear localization. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 67 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 756 The length of the canonical sequence.
Location on the sequence: help 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: help 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: 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 – 756 DNA mismatch repair protein Mlh1
Binding site 63 – 63
Alternative sequence 1 – 241 Missing. In isoform 2.
Alternative sequence 1 – 101 MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRG -> MAF. In isoform 3.



Literature citations
A cell-free assay for the functional analysis of variants of the mismatch repair protein MLH1.
Drost M.; Zonneveld J.B.; van Dijk L.; Morreau H.; Tops C.M.; Vasen H.F.; Wijnen J.T.; de Wind N.;
Hum. Mutat. 31:247-253(2010)
Cited for: CHARACTERIZATION OF VARIANTS LYNCH2 CYS-31; LYS-37; HIS-38; LYS-38; PHE-44; ARG-67; PRO-109; PRO-111; MET-117; CYS-265; SER-265; GLN-443; PRO-550; GLY-578; PHE-582; ASP-589; ALA-618; CYS-646; LEU-648; LEU-654 AND PRO-659; CHARACTERIZATION OF VARIANTS GLY-93; VAL-219; SER-403; ASN-406 AND MET-716; FUNCTION; 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 LYNCH2 LEU-28; SER-29; 45-THR--ILE-47 DELINS CYS-PHE; GLU-63; ARG-67; GLU-71 DEL; ARG-77; VAL-80; GLU-84; ARG-107; ARG-155; GLY-185; PRO-247; PRO-329; ILE-330 DEL; GLN-443; ALA-460; PRO-550; 578-GLU--GLU-632 DEL; ASP-589; VAL-612 DEL; LYS-616 DEL; ALA-618; THR-618; 633-GLU--GLU-663 DEL; CYS-646; LEU-648; SER-648; LEU-654; GLN-659; PRO-659; THR-681 AND TRP-687; CHARACTERIZATION OF VARIANTS GLY-93; MET-213; VAL-219 AND MET-716; SUBCELLULAR LOCATION; FUNCTION; Mutational analysis of the hMLH1 gene using an automated two-dimensional DNA typing system.
Sasaki S.; Tokino T.; Miyatsu T.; Muto T.; Nakamura Y.;
Hum. Mutat. 9:164-171(1997)
Cited for: VARIANT LYNCH2 ARG-67; VARIANT VAL-219; Excess of hMLH1 germline mutations in Swiss families with hereditary non-polyposis colorectal cancer.
Hutter P.; Couturier A.; Membrez V.; Joris F.; Sappino A.-P.; Chappuis P.O.;
Int. J. Cancer 78:680-684(1998)
Cited for: VARIANTS LYNCH2 ARG-67; ILE-262 DEL; THR-551 AND PHE-565; VARIANTS VAL-219 AND MET-716; Influence of selection criteria on mutation detection in patients with hereditary nonpolyposis colorectal cancer.
Heinimann K.; Scott R.J.; Buerstedde J.-M.; Weber W.; Siebold K.; Attenhofer M.; Mueller H.; Dobbie Z.;
Cancer 85:2512-2518(1999)
Cited for: VARIANTS LYNCH2 ARG-67; ARG-117 AND GLU-485; VARIANT VAL-219; Molecular analysis of hereditary nonpolyposis colorectal cancer in the United States: high mutation detection rate among clinically selected families and characterization of an American founder genomic deletion of the MSH2 gene.
Wagner A.; Barrows A.; Wijnen J.T.; van der Klift H.; Franken P.F.; Verkuijlen P.; Nakagawa H.; Geugien M.; Jaghmohan-Changur S.; Breukel C.; Meijers-Heijboer H.; Morreau H.; van Puijenbroek M.; Burn J.; Coronel S.; Kinarski Y.; Okimoto R.; Watson P.; Lynch J.F.; de la Chapelle A.; Lynch H.T.; Fodde R.;
Am. J. Hum. Genet. 72:1088-1100(2003)
Cited for: VARIANTS LYNCH2 SER-29; ARG-67; LEU-185 AND ASP-244; Mutation analysis of the MLH1, MSH2 and MSH6 genes in patients with double primary cancers of the colorectum and the endometrium: a population-based study in northern Sweden.
Cederquist K.; Emanuelsson M.; Goeransson I.; Holinski-Feder E.; Mueller-Koch Y.; Golovleva I.; Groenberg H.;
Int. J. Cancer 109:370-376(2004)
Cited for: VARIANTS LYNCH2 VAL-21; ARG-67; ASN-68 AND LYS-616 DEL; Functional significance and clinical phenotype of nontruncating mismatch repair variants of MLH1.
Raevaara T.E.; Korhonen M.K.; Lohi H.; Hampel H.; Lynch E.; Loennqvist K.E.; Holinski-Feder E.; Sutter C.; McKinnon W.; Duraisamy S.; Gerdes A.-M.; Peltomaeki P.; Kohonen-Corish M.; Mangold E.; Macrae F.; Greenblatt M.; de la Chapelle A.; Nystroem M.;
Gastroenterology 129:537-549(2005)
Cited for: VARIANTS LYNCH2 LEU-28; 45-THR--PHE-47 DELINS CYS-PHE; GLU-63; ARG-67; GLU-71 DEL; ARG-77; VAL-80; GLU-84; ARG-107; ARG-155; GLY-185; PRO-247; PRO-329; ILE-330 DEL; PRO-550; ASP-589; VAL-612 DEL; LYS-616 DEL; LEU-648; SER-648; LEU-654 AND PRO-659; VARIANTS SER-29; GLY-93; GLN-443; ALA-618; CYS-646; GLN-659; THR-681 AND MET-716; CHARACTERIZATION OF VARIANTS LYNCH2 LEU-28; 45-THR--PHE-47 DELINS CYS-PHE; GLU-63; ARG-67; GLU-71 DEL; ARG-77; VAL-80; GLU-84; ARG-107; ARG-155; GLY-185; PRO-247; PRO-329; ILE-330 DEL; PRO-550; ASP-589; VAL-612 DEL; LYS-616 DEL; THR-618; LEU-648; SER-648; LEU-654 AND PRO-659; CHARACTERIZATION OF VARIANTS SER-29; GLY-93; MET-213; VAL-219; GLN-443; ALA-618; CYS-646; GLN-659; THR-681 AND MET-716; 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 LYNCH2 LEU-28; LYS-35; ARG-67; VAL-111; MET-117; PRO-292; THR-441; LYS-618 DEL; PRO-623; ILE-657 DEL; THR-681; TRP-687 AND ARG-751; 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 LYNCH2 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; Functional characterization of MLH1 missense variants identified in Lynch syndrome patients.
Andersen S.D.; Liberti S.E.; Luetzen A.; Drost M.; Bernstein I.; Nilbert M.; Dominguez M.; Nystroem M.; Hansen T.V.; Christoffersen J.W.; Jaeger A.C.; de Wind N.; Nielsen F.C.; Toerring P.M.; Rasmussen L.J.;
Hum. Mutat. 33:1647-1655(2012)
Cited for: VARIANTS LYNCH2 CYS-233 DEL AND TRP-389; CHARACTERIZATION OF VARIANTS LYNCH2 LEU-28; LYS-37; HIS-38; LYS-38; PHE-44; ARG-67; PRO-109; PRO-111; MET-117; CYS-233 DEL; CYS-265; TRP-389; GLN-443; PRO-550; GLY-578; PHE-582; ASP-589; ALA-618; CYS-646; LEU-648; LEU-654; PRO-659 AND VAL-716 DEL; CHARACTERIZATION OF VARIANTS GLY-93; VAL-219; SER-403; ASN-406 AND MET-716; INTERACTION WITH PMS2; INTERACTION WITH EXO1; SUBCELLULAR LOCATION;
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.