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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P52701: Variant p.Ser144Ile

DNA mismatch repair protein Msh6
Gene: MSH6
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Variant information Variant position: help 144 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help US 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 Serine (S) to Isoleucine (I) at position 144 (S144I, p.Ser144Ile). 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 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: 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 LYNCH5 and CRC; uncertain significance; normal mismatch repair activity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 144 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1360 The length of the canonical sequence.
Location on the sequence: help GKSVRVHVQFFDDSPTRGWV S KRLLKPYTGSKSKEAQKGGH 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                         GKSVRVHVQFFDDSPTRGWVSKRLLKPYTGSKSKEAQKGGH

Mouse                         GKSVRVHVQFFDDSPTRGWVSKRMLKPYTGSKSKEAQKGGH

Chicken                       GSSARIHVQFFDVSPTRGWVSIKYLRPYKGSSDREVLKGGM

Drosophila                    -KSEKENLQ----------------------NQQPKVKDGK

Slime mold                    KSLPPSNFSL---------------------VVNEQEEENE

Baker's yeast                 VSTVRSDIMH----------------------SQEPQSDTM

Fission yeast                 SSPKRPHDSLGEESPGKLLR-----------TSVKQEPDSE

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 1 – 1360 DNA mismatch repair protein Msh6
Domain 92 – 154 PWWP
Modified residue 137 – 137 Phosphoserine
Alternative sequence 1 – 302 Missing. In isoform 4.
Alternative sequence 80 – 209 Missing. In isoform 3.
Beta strand 139 – 144



Literature citations
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 LYNCH5 LEU-128; ILE-144; ARG-566; LEU-623; THR-728; GLY-881 DELINS LYS-SER; THR-1087; HIS-1095; LYS-1193 AND GLN-1354; CHARACTERIZATION OF VARIANT ARG-1087; FUNCTION; Association of hereditary nonpolyposis colorectal cancer-related tumors displaying low microsatellite instability with MSH6 germline mutations.
Wu Y.; Berends M.J.W.; Mensink R.G.J.; Kempinga C.; Sijmons R.H.; van Der Zee A.G.J.; Hollema H.; Kleibeuker J.H.; Buys C.H.C.M.; Hofstra R.M.W.;
Am. J. Hum. Genet. 65:1291-1298(1999)
Cited for: VARIANTS LYNCH5 ILE-144 AND CYS-850; Molecular and clinical characteristics of MSH6 variants: an analysis of 25 index carriers of a germline variant.
Berends M.J.W.; Wu Y.; Sijmons R.H.; Mensink R.G.J.; van der Sluis T.; Hordijk-Hos J.M.; de Vries E.G.E.; Hollema H.; Karrenbeld A.; Buys C.H.C.M.; van der Zee A.G.J.; Hofstra R.M.W.; Kleibeuker J.H.;
Am. J. Hum. Genet. 70:26-37(2002)
Cited for: VARIANTS CRC ILE-144; ARG-522; MET-725; CYS-850; ALA-878; ASP-1021; MET-1100; ILE-1219 AND ASP-1248; 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 THR-13; LEU-65; ILE-144; HIS-468; CYS-503; LEU-580; ALA-878; LEU-1232 AND GLY-1321;
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.