UniProtKB/Swiss-Prot P40692: Variant p.Lys618Thr

DNA mismatch repair protein Mlh1
Gene: MLH1
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Variant information Variant position:

618 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 Lysine (K) to Threonine (T) at position 618 (K618T, p.Lys618Thr). 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 large size and basic (K) to medium size and polar (T) 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:

In LYNCH2; type II; loss of nuclear localization. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs63750449 [ dbSNP | Ensembl ]

Sequence information Variant position:

618 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:

TEEDGPKEGLAEYIVEFLKK K AEMLADYFSLEIDEEGNLIG 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                         TEEDGPKEGLAEYIVEFLKKKAEMLADYFSLEIDEEG--------NLIG

Mouse                         TEDDGPKEGLAEYIVEFLKKKAEMLADYFSVEIDEEG----

Rat                           TEEDGPKEGLAEYIVEFLKKKAKMLADYFSVEIDEEG----

Slime mold                    MESDGPKDKIADYLTKLLISKKELLNEYFSIEINEDG----

Baker's yeast                 LNDDASKEKIISKIWDM----SSMLNEYYSIELVNDGLDND

Fission yeast                 DEDKSESEKFTRLLVS----RRDMLKDYFSISVTSGG----

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	410 – 650	Interaction with EXO1
Helix	604 – 626

Literature citations
Genomic structure of human mismatch repair gene, hMLH1, and its mutation analysis in patients with hereditary non-polyposis colorectal cancer (HNPCC).
Han H.-J.; Maruyama M.; Baba S.; Park J.-G.; Nakamura Y.;
Hum. Mol. Genet. 4:237-242(1995)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS LYNCH2 LEU-542; PRO-574; VAL-582 AND THR-618; 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 LYNCH2 LEU-28; SER-29; 45-THR--ILE-47 DELINS CYS-PHE; GLU-63; ARG-67; GLU-71 DEL; ARG-77; VAL-80; GLU-84; ARG-107; ARG-155; GLY-185; PRO-247; PRO-329; ILE-330 DEL; GLN-443; ALA-460; PRO-550; 578-GLU--GLU-632 DEL; ASP-589; VAL-612 DEL; LYS-616 DEL; ALA-618; THR-618; 633-GLU--GLU-663 DEL; CYS-646; LEU-648; SER-648; LEU-654; GLN-659; PRO-659; THR-681 AND TRP-687; CHARACTERIZATION OF VARIANTS GLY-93; MET-213; VAL-219 AND MET-716; SUBCELLULAR LOCATION; FUNCTION; Microsatellite instability and mutation analysis of hMSH2 and hMLH1 in patients with sporadic, familial and hereditary colorectal cancer.
Moslein G.; Tester D.J.; Lindor N.M.; Honchel R.; Cunningham J.M.; French A.J.; Halling K.C.; Schwab M.; Goretzki P.; Thibodeau S.N.;
Hum. Mol. Genet. 5:1245-1252(1996)
Cited for: VARIANTS LYNCH2 LYS-616 DEL AND THR-618; VARIANT CRC THR-492; 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; hMLH1 and hMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancer.
Rossi B.M.; Lopes A.; Oliveira Ferreira F.; Nakagawa W.T.; Napoli Ferreira C.C.; Casali Da Rocha J.C.; Simpson C.C.; Simpson A.J.G.;
Ann. Surg. Oncol. 9:555-561(2002)
Cited for: VARIANTS LYNCH2 SER-338; ARG-603; THR-618 AND TYR-718; Pathogenicity of missense and splice site mutations in hMSH2 and hMLH1 mismatch repair genes: implications for genetic testing.
Cravo M.; Afonso A.J.; Lage P.; Albuquerque C.; Maia L.; Lacerda C.; Fidalgo P.; Chaves P.; Cruz C.; Nobre-Leitao C.;
Gut 50:405-412(2002)
Cited for: VARIANTS LYNCH2 CYS-385; HIS-607; THR-618 AND SER-648; VARIANT MET-213; Functional significance and clinical phenotype of nontruncating mismatch repair variants of MLH1.
Raevaara T.E.; Korhonen M.K.; Lohi H.; Hampel H.; Lynch E.; Loennqvist K.E.; Holinski-Feder E.; Sutter C.; McKinnon W.; Duraisamy S.; Gerdes A.-M.; Peltomaeki P.; Kohonen-Corish M.; Mangold E.; Macrae F.; Greenblatt M.; de la Chapelle A.; Nystroem M.;
Gastroenterology 129:537-549(2005)
Cited for: VARIANTS LYNCH2 LEU-28; 45-THR--PHE-47 DELINS CYS-PHE; GLU-63; ARG-67; GLU-71 DEL; ARG-77; VAL-80; GLU-84; ARG-107; ARG-155; GLY-185; PRO-247; PRO-329; ILE-330 DEL; PRO-550; ASP-589; VAL-612 DEL; LYS-616 DEL; LEU-648; SER-648; LEU-654 AND PRO-659; VARIANTS SER-29; GLY-93; GLN-443; ALA-618; CYS-646; GLN-659; THR-681 AND MET-716; CHARACTERIZATION OF VARIANTS LYNCH2 LEU-28; 45-THR--PHE-47 DELINS CYS-PHE; GLU-63; ARG-67; GLU-71 DEL; ARG-77; VAL-80; GLU-84; ARG-107; ARG-155; GLY-185; PRO-247; PRO-329; ILE-330 DEL; PRO-550; ASP-589; VAL-612 DEL; LYS-616 DEL; THR-618; LEU-648; SER-648; LEU-654 AND PRO-659; CHARACTERIZATION OF VARIANTS SER-29; GLY-93; MET-213; VAL-219; GLN-443; ALA-618; CYS-646; GLN-659; THR-681 AND MET-716;

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.