UniProtKB/Swiss-Prot P52701: Variant p.Ala20Val

DNA mismatch repair protein Msh6
Gene: MSH6
Chromosomal location: 2p16
Variant information

Variant position:  20
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Alanine (A) to Valine (V) at position 20 (A20V, p.Ala20Val).
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 hydrophobic (A) to medium size and hydrophobic (V)
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 colorectal/endometrial cancer and HNPCC5; repair proficient.
Any additional useful information about the variant.

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



Sequence information

Variant position:  20
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1360
The length of the canonical sequence.

Location on the sequence:   MSRQSTLYSFFPKSPALSD  A NKASARASREGGRAAAAPGA
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                         MSRQSTLYSFFPK-SPALSDANKASARASREGGRAAAAPGA

Mouse                         MSRQSTLYSFFPK-SPALGDTKKAAAEASRQG---AAASG

Drosophila                    GTPTNTLLNYFSK------------------------SPA

Slime mold                    PIIEEGFDSFFDD-IPT-EELEPDLNSIPISSSQQTSTSN

Baker's yeast                 KMKQSSLLSFFSKQVPS-------------------GTPS

Fission yeast                 KTKQKTLFGFFSK-IPNVKQEKSDSTL--------SSSSN

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 1 – 1360 DNA mismatch repair protein Msh6
Modified residue 14 – 14 Phosphoserine
Alternative sequence 1 – 302 Missing. In isoform 4.


Literature citations

Do MSH6 mutations contribute to double primary cancers of the colorectum and endometrium?
Charames G.S.; Millar A.L.; Pal T.; Narod S.; Bapat B.;
Hum. Genet. 107:623-629(2000)
Cited for: VARIANTS COLORECTAL/ENDOMETRIAL CANCER VAL-20; ALA-878 AND HIS-901;

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 VARIANT HNPCC5 VAL-20; CHARACTERIZATION OF VARIANTS CRC HIS-976 AND ASP-1021; CHARACTERIZATION OF VARIANTS SER-25; VAL-326; VAL-396; VAL-492; CYS-503; ARG-522; ASN-610; CYS-850; ALA-878; TYR-1026; SER-1087 AND MET-1225;

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.