UniProtKB/Swiss-Prot P40692: Variant p.Asn64Ser

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

64 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 Asparagine (N) to Serine (S) at position 64 (N64S, p.Asn64Ser). 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 medium size and polar (N) to small size and polar (S) 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. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs63750952 [ dbSNP | Ensembl ]

Sequence information Variant position:

64 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:

STSIQVIVKEGGLKLIQIQD N GTGIRKEDLDIVCERFTTSK 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                         STSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSK

Mouse                         STNIQVVVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSK

Rat                           STNIQVIVREGGLKLIQIQDNGTGIRKEDLDIVCERFTTSK

Slime mold                    STTITVTVKDGGMKFLQIQDNGSGIRLEDMGIVCERFTTSK

Baker's yeast                 ATMIDILVKEGGIKVLQITDNGSGINKADLPILCERFTTSK

Fission yeast                 STSIDVLLKDGGLKLLQITDNGSGIQYDDLPYLCQRFSTSK

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
Binding site	63 – 63
Alternative sequence	1 – 241	Missing. In isoform 2.
Alternative sequence	1 – 101	MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRG -> MAF. In isoform 3.

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 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; Hereditary nonpolyposis colorectal cancer families not complying with the Amsterdam criteria show extremely low frequency of mismatch-repair-gene mutations.
Wijnen J.; Khan P.M.; Vasen H.; van der Klift H.; Mulder A.; van Leeuwen-Cornelisse I.; Bakker B.; Losekoot M.; Moeller P.; Fodde R.;
Am. J. Hum. Genet. 61:329-335(1997)
Cited for: VARIANTS LYNCH2 LYS-62; SER-64; LYS-616 DEL; ALA-618 AND PRO-659; CHARACTERIZATION OF VARIANT LYNCH2 LYS-62; FUNCTION; 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; HNPCC mutation MLH1 P648S makes the functional protein unstable, and homozygosity predisposes to mild neurofibromatosis type 1.
Raevaara T.E.; Gerdes A.-M.; Loennqvist K.E.; Tybjaerg-Hansen A.; Abdel-Rahman W.M.; Kariola R.; Peltomaeki P.; Nystroem-Lahti M.;
Genes Chromosomes Cancer 40:261-265(2004)
Cited for: VARIANT LYNCH2 SER-648; Germline mutations in MLH1, MSH2 and MSH6 in Korean hereditary non-polyposis colorectal cancer families.
Shin Y.-K.; Heo S.-C.; Shin J.-H.; Hong S.-H.; Ku J.-L.; Yoo B.-C.; Kim I.-J.; Park J.-G.;
Hum. Mutat. 24:351-351(2004)
Cited for: VARIANTS LYNCH2 CYS-217; GLY-282; LEU-542; PRO-542; PRO-549; PRO-574; PRO-636; SER-640 AND MET-724; 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; A large fraction of unclassified variants of the mismatch repair genes MLH1 and MSH2 is associated with splicing defects.
Tournier I.; Vezain M.; Martins A.; Charbonnier F.; Baert-Desurmont S.; Olschwang S.; Wang Q.; Buisine M.P.; Soret J.; Tazi J.; Frebourg T.; Tosi M.;
Hum. Mutat. 29:1412-1424(2008)
Cited for: VARIANT LYNCH2 ILE-330 DEL; VARIANTS HIS-41; ARG-67; ARG-77; SER-98; SER-101; ASP-101; LYS-116; MET-117; ASN-126; MET-213; SER-215; SER-216; PHE-260; CYS-265; HIS-265; ASP-320; ALA-326; ILE-330 DEL; TRP-474; GLN-474; ASP-539; PRO-549; THR-551; ARG-585; ARG-603; HIS-607; PRO-619; SER-640; LEU-640; VAL-655; SER-656; ARG-666; THR-681 AND ARG-689;

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.