UniProtKB/SwissProt variant VAR

Variant information

Variant position:

423

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 Alanine (A) to Threonine (T) at position 423 (A423T, p.Ala423Thr).

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 polar (T)

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:

Normal DNA mismatch repair activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs587778619 [ dbSNP | Ensembl ]

Sequence information

Variant position:

423

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

Protein sequence length:

862

The length of the canonical sequence.

Location on the sequence:

SPSLRTGEEKKDVSISRLRE A FSLRHTTENKPHSPKTPEPR

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                         SPSLR-TGEEKKDVSISRLREAFSLRHTTENKPHSPKTPEPR

Mouse                         SPSLKSTADEKRVASISRLREAFSLHPTKEIKSRGPETAEL

Chicken                       SETENPSSEGKRVMTLSRLRESFSLHQT-ESYFQSPKKVKQ

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	1 – 862	Mismatch repair endonuclease PMS2
Region	391 – 552	Disordered
Compositional bias	391 – 440	Basic and acidic residues
Alternative sequence	184 – 862	Missing. In isoform 4.
Alternative sequence	269 – 669	Missing. In isoform 2.

Literature citations

Functional PMS2 hybrid alleles containing a pseudogene-specific missense variant trace back to a single ancient intrachromosomal recombination event.
Ganster C.; Wernstedt A.; Kehrer-Sawatzki H.; Messiaen L.; Schmidt K.; Rahner N.; Heinimann K.; Fonatsch C.; Zschocke J.; Wimmer K.;
Hum. Mutat. 31:552-560(2010)
Cited for: VARIANTS THR-423; MET-511 AND PRO-511;

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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P54278: Variant p.Ala423Thr