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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P40692: Variant p.Ile219Val

DNA mismatch repair protein Mlh1
Gene: MLH1
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Variant information Variant position: help 219 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LB/B 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 Isoleucine (I) to Valine (V) at position 219 (I219V, p.Ile219Val). 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 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: help 3 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 No decrease in mismatch repair activity; no effect on 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 219 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 ETVADVRTLPNASTVDNIRS I FGNAVSRELIEIGCEDKTLA 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                         ETVADVRTLPNASTVDN--IRSIFGNAVSRELIEIGCEDKT-----------------------LA

Mouse                         ETVSDVRTLPNATTVDN--IRSIFGNAVSRELIEVGCEDKT

Rat                           ETVSDVRTLPNATTVDN--IRSIFGNAVSRELIEVGCEDKT

Slime mold                    DPTPEVHTSGGQNSLEKDVIGSLYGTDLSKELKIITIDPNN

Baker's yeast                 DSNYSLSVKPSYTVQDR--IRTVFNKSVASNLITFHISKVE

Fission yeast                 DTVASLSLSSRLSKADK--IRHIYGPRVASHLRDFSLGEGQ

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
Alternative sequence 1 – 241 Missing. In isoform 2.
Helix 212 – 220



Literature citations
Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS VAL-32; MET-213 AND VAL-219; 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; MSH2 and MLH1 mutations in sporadic replication error-positive colorectal carcinoma as assessed by two-dimensional DNA electrophoresis.
Wu Y.; Nystroem-Lahti M.; Osinga J.; Looman M.W.G.; Peltomaeki P.; Aaltonen L.A.; de la Chapelle A.; Hofstra R.M.W.; Buys C.H.C.M.;
Genes Chromosomes Cancer 18:269-278(1997)
Cited for: VARIANTS CRC GLU-54; VAL-244 AND GLN-325; VARIANTS VAL-219 AND ASN-406; Mean age of tumor onset in hereditary nonpolyposis colorectal cancer (HNPCC) families correlates with the presence of mutations in DNA mismatch repair genes.
Pensotti V.; Radice P.; Presciuttini S.; Calistri D.; Gazzoli I.; Grimalt Perez A.P.; Mondini P.; Buonsanti G.; Sala P.; Rossetti C.; Ranzani G.N.; Bertario L.; Pierotti M.A.;
Genes Chromosomes Cancer 19:135-142(1997)
Cited for: VARIANTS LYNCH2 PRO-128 AND ASP-244; VARIANT VAL-219; 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; Germline HNPCC gene variants have little influence on the risk for sporadic colorectal cancer.
Tomlinson I.P.M.; Beck N.E.; Homfray T.; Harocopos C.J.; Bodmer W.F.;
J. Med. Genet. 34:39-42(1997)
Cited for: VARIANT CRC TYR-77; 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; Enhanced detection of deleterious and other germline mutations of hMSH2 and hMLH1 in Japanese hereditary nonpolyposis colorectal cancer kindreds.
Nomura S.; Sugano K.; Kashiwabara H.; Taniguchi T.; Fukayama N.; Fujita S.; Akasu T.; Moriya Y.; Ohhigashi S.; Kakizoe T.; Sekiya T.;
Biochem. Biophys. Res. Commun. 271:120-129(2000)
Cited for: VARIANTS LYNCH2 VAL-111 AND PRO-588; VARIANTS VAL-219 AND ASP-384; Microsatellite instability and mutation analysis of candidate genes in unselected Sardinian patients with endometrial carcinoma.
Baldinu P.; Cossu A.; Manca A.; Satta M.P.; Pisano M.; Casula M.; Dessole S.; Pintus A.; Tanda F.; Palmieri G.;
Cancer 94:3157-3168(2002)
Cited for: VARIANTS VAL-219 AND VAL-655; Functional analysis of hMLH1 variants and HNPCC-related mutations using a human expression system.
Trojan J.; Zeuzem S.; Randolph A.; Hemmerle C.; Brieger A.; Raedle J.; Plotz G.; Jiricny J.; Marra G.;
Gastroenterology 122:211-219(2002)
Cited for: CHARACTERIZATION OF VARIANTS LYNCH2 MET-117; GLY-185; CYS-217; ASP-244 AND ALA-326; CHARACTERIZATION OF VARIANTS VAL-219 AND HIS-265; Seven novel MLH1 and MSH2 germline mutations in hereditary nonpolyposis colorectal cancer.
Krueger S.; Plaschke J.; Pistorius S.; Jeske B.; Haas S.; Kraemer H.; Hinterseher I.; Bier A.; Kreuz F.R.; Theissig F.; Saeger H.D.; Schackert H.K.;
Hum. Mutat. 19:82-82(2002)
Cited for: VARIANT LYNCH2 PRO-662; VARIANT VAL-219; Impact of microsatellite testing and mismatch repair protein expression on the clinical interpretation of genetic testing in hereditary non-polyposis colorectal cancer.
Ward R.; Meldrum C.; Williams R.; Mokany E.; Scott R.; Turner J.; Hawkins N.; Burgess B.; Groombridge C.; Spigelman A.;
J. Cancer Res. Clin. Oncol. 128:403-411(2002)
Cited for: VARIANTS LYNCH2 MET-117 AND PRO-247; VARIANTS VAL-219; ALA-618 AND MET-716; Germline MSH2 and MLH1 mutational spectrum in HNPCC families from Poland and the Baltic States.
Kurzawski G.; Suchy J.; Kladny J.; Safranow K.; Jakubowska A.; Elsakov P.; Kucinskas V.; Gardovski J.; Irmejs A.; Sibul H.; Huzarski T.; Byrski T.; Debniak T.; Cybulski C.; Gronwald J.; Oszurek O.; Clark J.; Gozdz S.; Niepsuj S.; Slomski R.; Plawski A.; Lacka-Wojciechowska A.; Rozmiarek A.; Fiszer-Maliszewska L.; Bebenek M.; Sorokin D.; Stawicka M.; Godlewski D.; Richter P.; Brozek I.; Wysocka B.; Jawien A.; Banaszkiewicz Z.; Kowalczyk J.; Czudowska D.; Goretzki P.E.; Moeslein G.; Lubinski J.;
J. Med. Genet. 39:E65-E65(2002)
Cited for: VARIANTS LYNCH2 PHE-19; LEU-28; MET-117; PRO-292; THR-681 AND TRP-687; VARIANT VAL-219; 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; 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.