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UniProtKB/Swiss-Prot P43246: Variant p.Leu390Phe

DNA mismatch repair protein Msh2
Gene: MSH2
Variant information

Variant position:  390
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 Leucine (L) to Phenylalanine (F) at position 390 (L390F, p.Leu390Phe).
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 medium size and hydrophobic (L) to large size and aromatic (F)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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 and CRC; unknown pathological significance; may decrease mismatch repair activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  390
The position of the amino-acid change on the UniProtKB canonical protein sequence.

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

Location on the sequence:   AELRQTLQEDLLRRFPDLNR  L AKKFQRQAANLQDCYRLYQG
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                         AELRQTLQED--LLRRFPDLNRLAKKFQRQAANLQDCYRLYQG

Mouse                         SELRQSLQED--LLRRFPDLNRLAKKFQRQAANLQDCYRLY

Rat                           SELRRALQED--LLRRFPDLNRLAKKFQRQAANLQDCYRLY

Bovine                        AELRQNLQED--LLRRFPDLNRLAKKFQRQAANLQDCYRLY

Drosophila                    PDTMETLSLD--YLKRIPDILMLTKKLMRRKANLQDLFRIY

Slime mold                    LELRQSLRSN--DLKKIGDLDRLSKKLHGQKATLEDCVNLY

Baker's yeast                 IELRQMLTSE--YLPMIPDIRRLTKKLNKR-GNLEDVLKIY

Fission yeast                 AEARQLLLDDDHLLRSIPDIPKLCRRLTRGSASLEDVVRIY

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 – 934 DNA mismatch repair protein Msh2
Helix 387 – 395


Literature citations

Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS MET-8; CYS-43; SER-127; ASP-322 AND PHE-390;

Molecular nature of colon tumors in hereditary nonpolyposis colon cancer, familial polyposis, and sporadic colon cancer.
Konishi M.; Kikuchi-Yanoshita R.; Tanaka K.; Muraoka M.; Onda A.; Okumura Y.; Kishi N.; Iwama T.; Mori T.; Koike M.; Ushio K.; Chiba M.; Nomizu S.; Konishi F.; Utsunomiya J.; Miyaki M.;
Gastroenterology 111:307-317(1996)
Cited for: VARIANTS PHE-390 AND LYS-419;

Novel germline mutations of hMSH2 in a patient with hereditary nonpolyposis colorectal cancer 'HNPCC' and in a patient with six primary cancers.
Okamura S.; Koyama K.; Miyoshi Y.; Monden M.; Takami M.;
J. Hum. Genet. 43:143-145(1998)
Cited for: VARIANT HNPCC1 PHE-390;

Mutator phenotypes of common polymorphisms and missense mutations in MSH2.
Drotschmann K.; Clark A.B.; Kunkel T.A.;
Curr. Biol. 9:907-910(1999)
Cited for: CHARACTERIZATION OF VARIANTS ASP-322; PHE-390; LYS-419; TYR-506; PRO-524; LEU-622 AND PHE-697;

Novel hMLH1 and hMSH2 germline mutations in African Americans with colorectal cancer.
Weber T.K.; Chin H.-M.; Rodriguez-Bigas M.; Keitz B.; Gilligan R.; O'Malley L.; Urf E.; Diba N.; Pazik J.; Petrelli N.J.;
JAMA 281:2316-2320(1999)
Cited for: VARIANT HNPCC1 PHE-390;

Oncogenic pathway of sporadic colorectal cancer with novel germline missense mutations in the hMSH2 gene.
Yamada K.; Zhong X.; Kanazawa S.; Koike J.; Tsujita K.; Hemmi H.;
Oncol. Rep. 10:859-866(2003)
Cited for: VARIANTS CRC SER-40; VAL-169; ARG-203; PHE-390; LYS-419; CYS-619 AND ARG-629; VARIANT MET-8;

Clinical and molecular characteristics of hereditary non-polyposis colorectal cancer families in Southeast Asia.
Lee S.-C.; Guo J.-Y.; Lim R.; Soo R.; Koay E.; Salto-Tellez M.; Leong A.; Goh B.-C.;
Clin. Genet. 68:137-145(2005)
Cited for: VARIANTS HNPCC1 VAL-169; PHE-390; ALA-564 AND ARG-629; VARIANT CRC LYS-419;

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;

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 HNPCC1 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.