UniProtKB/Swiss-Prot P40692: Variant p.Ser406Asn

DNA mismatch repair protein Mlh1
Gene: MLH1
Feedback?

Variant information Variant position:

406 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 Serine (S) to Asparagine (N) at position 406 (S406N, p.Ser406Asn). 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 polar (N) 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
Variant description:

No decrease in mismatch repair activity; no effect on nuclear localization. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs41294980 [ dbSNP | Ensembl ]

Sequence information Variant position:

406 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

756 The length of the canonical sequence.
Location on the sequence:

TDSREQKLDAFLQPLSKPLS S QPQAIVTEDKTDISSGRARQ 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                         TDSREQKLDAFLQPL---SKPLSSQPQAIVT--E--DKTDISSGRA----RQ

Mouse                         TDSREQKLDAFLQPV---SSLGPSQPQDPAPVRG--ARTEG

Rat                           TDSRDQKLDAFMQPV---SRRLPSQPQDPVP--G--NRTEG

Slime mold                    SDSKSQTLDAFLNPMDYNNNNDSSIDDNDGSGIGRYDDVDG

Baker's yeast                 IDASQAKITSFLSSSQQFNFEGSS------------TKRQL

Fission yeast                 TDPRERSIKSMLS----------------------------

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 – 756	DNA mismatch repair protein Mlh1
Region	400 – 491	Disordered
Compositional bias	400 – 416	Polar residues

Literature citations
A cell-free assay for the functional analysis of variants of the mismatch repair protein MLH1.
Drost M.; Zonneveld J.B.; van Dijk L.; Morreau H.; Tops C.M.; Vasen H.F.; Wijnen J.T.; de Wind N.;
Hum. Mutat. 31:247-253(2010)
Cited for: CHARACTERIZATION OF VARIANTS LYNCH2 CYS-31; LYS-37; HIS-38; LYS-38; PHE-44; ARG-67; PRO-109; PRO-111; MET-117; CYS-265; SER-265; GLN-443; PRO-550; GLY-578; PHE-582; ASP-589; ALA-618; CYS-646; LEU-648; LEU-654 AND PRO-659; CHARACTERIZATION OF VARIANTS GLY-93; VAL-219; SER-403; ASN-406 AND MET-716; FUNCTION; 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: VARIANTS CRC GLU-54; VAL-244 AND GLN-325; VARIANTS VAL-219 AND ASN-406; 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 HIS-265; ALA-326; PRO-385; ASN-406; THR-618 AND MET-716; 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 CRC GLU-67 AND THR-681; VARIANTS ALA-22; GLY-93; SER-309; ASN-406; HIS-607; ALA-618; ARG-689; MET-716; TYR-718 AND ARG-751; Functional characterization of MLH1 missense variants identified in Lynch syndrome patients.
Andersen S.D.; Liberti S.E.; Luetzen A.; Drost M.; Bernstein I.; Nilbert M.; Dominguez M.; Nystroem M.; Hansen T.V.; Christoffersen J.W.; Jaeger A.C.; de Wind N.; Nielsen F.C.; Toerring P.M.; Rasmussen L.J.;
Hum. Mutat. 33:1647-1655(2012)
Cited for: VARIANTS LYNCH2 CYS-233 DEL AND TRP-389; CHARACTERIZATION OF VARIANTS LYNCH2 LEU-28; LYS-37; HIS-38; LYS-38; PHE-44; ARG-67; PRO-109; PRO-111; MET-117; CYS-233 DEL; CYS-265; TRP-389; GLN-443; PRO-550; GLY-578; PHE-582; ASP-589; ALA-618; CYS-646; LEU-648; LEU-654; PRO-659 AND VAL-716 DEL; CHARACTERIZATION OF VARIANTS GLY-93; VAL-219; SER-403; ASN-406 AND MET-716; INTERACTION WITH PMS2; INTERACTION WITH EXO1; SUBCELLULAR LOCATION;

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.