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UniProtKB/Swiss-Prot P54278: Variant p.Ser46Ile

Mismatch repair endonuclease PMS2
Gene: PMS2
Variant information

Variant position:  46
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  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:  From Serine (S) to Isoleucine (I) at position 46 (S46I, p.Ser46Ile).
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 small size and polar (S) to medium size and hydrophobic (I)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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:  In MMRCS4 and HNPCC4; strongly decreased DNA mismatch repair activity; no effect on protein abundance; no effect on subcellular localization.
Any additional useful information about the variant.

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

Sequence information

Variant position:  46
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  862
The length of the canonical sequence.

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.




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.

Chain 1 – 862 Mismatch repair endonuclease PMS2
Mutagenesis 41 – 41 E -> A. Decreased DNA mismatch repair activity.
Helix 35 – 48

Literature citations

Novel biallelic mutations in MSH6 and PMS2 genes: gene conversion as a likely cause of PMS2 gene inactivation.
Auclair J.; Leroux D.; Desseigne F.; Lasset C.; Saurin J.C.; Joly M.O.; Pinson S.; Xu X.L.; Montmain G.; Ruano E.; Navarro C.; Puisieux A.; Wang Q.;
Hum. Mutat. 28:1084-1090(2007)
Cited for: VARIANT MMRCS4 ILE-46;

The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations.
Senter L.; Clendenning M.; Sotamaa K.; Hampel H.; Green J.; Potter J.D.; Lindblom A.; Lagerstedt K.; Thibodeau S.N.; Lindor N.M.; Young J.; Winship I.; Dowty J.G.; White D.M.; Hopper J.L.; Baglietto L.; Jenkins M.A.; de la Chapelle A.;
Gastroenterology 135:419-428(2008)
Cited for: VARIANTS HNPCC4 ASN-46; ILE-46; PRO-205; ILE-622; ALA-663; LYS-705; ASP-750 AND TYR-843; VARIANT LEU-563;

Inactivation of DNA mismatch repair by variants of uncertain significance in the PMS2 gene.
Drost M.; Koppejan H.; de Wind N.;
Hum. Mutat. 34:1477-1480(2013)
Cited for: CHARACTERIZATION OF VARIANTS VAL-18; GLN-20; ALA-41; GLU-60; THR-423; LYS-485; ALA-511; MET-511; GLU-541; LEU-563; ILE-571; SER-597 AND ALA-857; CHARACTERIZATION OF VARIANTS HNPCC4 ASN-46; ILE-46; PRO-205; GLU-207; VAL-263; GLN-479; ILE-622; ALA-663; LYS-705; ASP-750; ARG-797 AND TYR-843; MUTAGENESIS OF GLU-41 AND TYR-519;

Refining the role of PMS2 in Lynch syndrome: germline mutational analysis improved by comprehensive assessment of variants.
Borras E.; Pineda M.; Cadinanos J.; Del Valle J.; Brieger A.; Hinrichsen I.; Cabanillas R.; Navarro M.; Brunet J.; Sanjuan X.; Musulen E.; van der Klift H.; Lazaro C.; Plotz G.; Blanco I.; Capella G.;
J. Med. Genet. 50:552-563(2013)

Comprehensive mutation analysis of PMS2 in a large cohort of probands suspected of lynch syndrome or constitutional mismatch repair deficiency syndrome.
van der Klift H.M.; Mensenkamp A.R.; Drost M.; Bik E.C.; Vos Y.J.; Gille H.J.; Redeker B.E.; Tiersma Y.; Zonneveld J.B.; Garcia E.G.; Letteboer T.G.; Olderode-Berends M.J.; van Hest L.P.; van Os T.A.; Verhoef S.; Wagner A.; van Asperen C.J.; Ten Broeke S.W.; Hes F.J.; de Wind N.; Nielsen M.; Devilee P.; Ligtenberg M.J.; Wijnen J.T.; Tops C.M.;
Hum. Mutat. 37:1162-1179(2016)
Cited for: VARIANTS MMRCS4 ILE-46; THR-66; TRP-107; GLY-115; PRO-205; VAL-263; LYS-307; SER-437; GLN-479; VAL-488; GLN-504; ILE-585 AND LEU-815; CHARACTERIZATION OF VARIANTS MMRCS4 ILE-46; THR-66; TRP-107; GLY-115; LYS-307; SER-437; VAL-488; GLN-504 AND LEU-815; VARIANTS VAL-18; GLU-60; SER-470; LEU-563; ILE-571 AND SER-775; CHARACTERIZATION OF VARIANTS SER-470 AND SER-775;

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.