UniProtKB/Swiss-Prot P43246: Variant p.Gly322Asp

DNA mismatch repair protein Msh2
Gene: MSH2
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Variant information Variant position:

322 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

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:

From Glycine (G) to Aspartate (D) at position 322 (G322D, p.Gly322Asp). 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 glycine (G) to medium size and acidic (D) 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
Other resources:

Links to websites of interest for the variant.

Variant rs4987188 [ dbSNP | Ensembl ]

Sequence information Variant position:

322 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:

LDIAAVRALNLFQGSVEDTT G SQSLAALLNKCKTPQGQRLV 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                         LDIAAVRALNLFQ-----------------GSVEDTTGSQSLAALLNKCKTPQGQRLV

Mouse                         LDMAAVRALNLFQ-----------------GSVEDTTGSQS

Rat                           LDMAAVRALNLFQ-----------------GSVEDTTGSQS

Bovine                        LDIAAVRALNLFQ-----------------GSVEDTSGSQS

Drosophila                    LDSAAVAALNIMP-------------KPGTHPSMPSYRWQS

Slime mold                    LDSSSFKGLHIIDLKDSSVSAAAGGGGAG-GASSSSNKDQS

Baker's yeast                 LDASAIKALNLFPQGPQNPFGSNNLAVSGFTSAGNSGKVTS

Fission yeast                 LDIAAVRSLNLLP-----------------PPNGNAHKTMS

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.

Type	Positions	Description
Chain	2 – 934	DNA mismatch repair protein Msh2

Literature citations
Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS MET-8; CYS-43; SER-127; ASP-322 AND PHE-390; 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 LYNCH1 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; CpG dinucleotides in the hMSH2 and hMLH1 genes are hotspots for HNPCC mutations.
Maliaka Y.K.; Chudina A.P.; Belev N.F.; Alday P.; Bochkov N.P.; Buerstedde J.-M.;
Hum. Genet. 97:251-255(1996)
Cited for: VARIANT ASP-322; 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: VARIANT ASP-322; Hereditary nonpolyposis colorectal cancer (HNPCC): eight novel germline mutations in hMSH2 or hMLH1 genes.
Wehner M.; Buschhausen L.; Lamberti C.; Kruse R.; Caspari R.; Propping P.; Friedl W.;
Hum. Mutat. 10:241-244(1997)
Cited for: VARIANT LYNCH1 PHE-697; VARIANT ASP-322; MSH2 codon 322 Gly to Asp seems not to confer an increased risk for colorectal cancer susceptibility.
Liu T.; Stathopoulos P.; Lindblom P.; Rubio C.; Wasteson Arver B.; Iselius L.; Holmberg E.; Groenberg H.; Lindblom A.;
Eur. J. Cancer 34:1981-1981(1998)
Cited for: VARIANT ASP-322; 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; Assessment of pathogenicity criteria for constitutional missense mutations of the hereditary nonpolyposis colorectal cancer genes MLH1 and MSH2.
Genuardi M.; Carrara S.; Anti M.; Ponz de Leon M.; Viel A.;
Eur. J. Hum. Genet. 7:778-782(1999)
Cited for: VARIANTS LYNCH1 GLN-246; SER-596 AND THR-834; VARIANT ASP-322; Detection of mutations in mismatch repair genes in Portuguese families with hereditary non-polyposis colorectal cancer (HNPCC) by a multi-method approach.
Fidalgo P.; Almeida M.R.; West S.; Gaspar C.; Maia L.; Wijnen J.; Albuquerque C.; Curtis A.; Cravo M.; Fodde R.; Leitao C.N.; Burn J.;
Eur. J. Hum. Genet. 8:49-53(2000)
Cited for: VARIANT ASP-322; Population-based molecular detection of hereditary nonpolyposis colorectal cancer.
Salovaara R.; Loukola A.; Kristo P.; Kaeaeriaeinen H.; Ahtola H.; Eskelinen M.; Haerkoenen N.; Julkunen R.; Kangas E.; Ojala S.; Tulikoura J.; Valkamo E.; Jaervinen H.; Mecklin J.-P.; Aaltonen L.A.; de la Chapelle A.;
J. Clin. Oncol. 18:2193-2200(2000)
Cited for: VARIANT LYNCH1 ASN-603; VARIANT ASP-322; Functional analysis of human MLH1 and MSH2 missense variants and hybrid human-yeast MLH1 proteins in Saccharomyces cerevisiae.
Ellison A.R.; Lofing J.; Bitter G.A.;
Hum. Mol. Genet. 10:1889-1900(2001)
Cited for: CHARACTERIZATION OF VARIANTS ASP-322; LEU-622 AND TYR-639; Pathogenicity of missense and splice site mutations in hMSH2 and hMLH1 mismatch repair genes: implications for genetic testing.
Cravo M.; Afonso A.J.; Lage P.; Albuquerque C.; Maia L.; Lacerda C.; Fidalgo P.; Chaves P.; Cruz C.; Nobre-Leitao C.;
Gut 50:405-412(2002)
Cited for: VARIANT ASP-322; 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 LYNCH1 ILE-102; ASP-163 AND ALA-564; VARIANT ASP-322; 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 LYNCH1 LEU-92 DEL AND ALA-853; VARIANT ASP-322; Microsatellite instability and mutation analysis among southern Italian patients with colorectal carcinoma: detection of different alterations accounting for MLH1 and MSH2 inactivation in familial cases.
Colombino M.; Cossu A.; Arba A.; Manca A.; Curci A.; Avallone A.; Comella G.; Botti G.; Scintu F.; Amoruso M.; D'Abbicco D.; d'Agnessa M.R.; Spanu A.; Tanda F.; Palmieri G.;
Ann. Oncol. 14:1530-1536(2003)
Cited for: VARIANTS CRC ILE-13 AND ILE-342; VARIANT ASP-322; 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 LYNCH1 THR-2; LEU-92 DEL; MET-145; PHE-390 AND ALA-853; VARIANT ASP-322; Classification of ambiguous mutations in DNA mismatch repair genes identified in a population-based study of colorectal cancer.
Barnetson R.A.; Cartwright N.; van Vliet A.; Haq N.; Drew K.; Farrington S.; Williams N.; Warner J.; Campbell H.; Porteous M.E.; Dunlop M.G.;
Hum. Mutat. 29:367-374(2008)
Cited for: VARIANTS GLN-46; LYS-106; ASP-322; SER-596; LEU-670; ILE-779; SER-807; HIS-835 AND ARG-911; Mechanisms of pathogenicity in human MSH2 missense mutants.
Ollila S.; Dermadi Bebek D.; Jiricny J.; Nystroem M.;
Hum. Mutat. 29:1355-1363(2008)
Cited for: CHARACTERIZATION OF VARIANTS LYNCH1 PRO-33; SER-127; ASP-161; ARG-162; ARG-164; PRO-173; PRO-187; VAL-272; TYR-333; ASN-603; PRO-636; ALA-674; PHE-697; 745-ILE-ILE-746 DEL; LYS-749; THR-834 AND GLU-923; CHARACTERIZATION OF 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;

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