UniProtKB/Swiss-Prot P52701: Variant p.Lys99Asn

DNA mismatch repair protein Msh6
Gene: MSH6
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Variant information Variant position:

99 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Asparagine (N) at position 99 (K99N, p.Lys99Asn). 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 (N) 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 CRC; uncertain significance. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs63751258 [ dbSNP | Ensembl ]

Sequence information Variant position:

99 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:

SVAPAAPTSCDFSPGDLVWA K MEGYPWWPCLVYNHPFDGTF 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                         SVAPA---APTSCDFSPGDLVWAKMEGYPW-WPCLVY-NHPFDGTF

Mouse                         ASSSAQAVPPSSCDFSPGDLVWAKMEGYPW-WPCLVY-NHP

Chicken                       SGV-----------YSPGDLVWAKMEGYPW-WPCLIY-NHP

Drosophila                    -----------------------------------------

Slime mold                    TTTTN---------------TNSQIPKAPT-TPSKLKLPTS

Baker's yeast                 ------------------DKITKNPQGGKT-GKLFVDVDED

Fission yeast                 NKNSS--SPERELPTSPSHHANTEIDSSSSMLPPPSSDPFS

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 – 1360	DNA mismatch repair protein Msh6
Domain	92 – 154	PWWP
Modified residue	79 – 79	Phosphoserine
Modified residue	91 – 91	Phosphoserine
Alternative sequence	1 – 302	Missing. In isoform 4.
Alternative sequence	80 – 209	Missing. In isoform 3.
Mutagenesis	103 – 103	Y -> A. Abolishes binding to H3K36me3 and DNA mismatch repair activity.

Literature citations
Lower incidence of colorectal cancer and later age of disease onset in 27 families with pathogenic MSH6 germline mutations compared with families with MLH1 or MSH2 mutations: the German hereditary nonpolyposis colorectal cancer consortium.
Plaschke J.; Engel C.; Krueger S.; Holinski-Feder E.; Pagenstecher C.; Mangold E.; Moeslein G.; Schulmann K.; Gebert J.; von Knebel Doeberitz M.; Rueschoff J.; Loeffler M.; Schackert H.K.;
J. Clin. Oncol. 22:4486-4494(2004)
Cited for: VARIANTS CRC ASN-99; ASP-619; VAL-787; ALA-878 AND CYS-1076;

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.