UniProtKB/Swiss-Prot P00451 : Variant p.Arg301His
Coagulation factor VIII
Gene: F8
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Variant information
Variant position:
301
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
LP/P [Disclaimer : Variants classification is intended for research purposes only, not for clinical and diagnostic use . The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant. ]
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 Arginine (R) to Histidine (H) at position 301 (R301H, p.Arg301His).
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 (R) to medium size and polar (H)
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 HEMA; severe.
Any additional useful information about the variant.
Other resources:
Links to websites of interest for the variant.
Sequence information
Variant position:
301
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:
2351
The length of the canonical sequence.
Location on the sequence:
TTPEVHSIFLEGHTFLVRNH
R QASLEISPITFLTAQTLLMD
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 TTPEVHSIFLEGHTFLVRNHR QASLEISPITFLTAQTLLMD
TTPEVHSIFLEGHTFLVRNHR QASLEISPITFLTAQTFLMD
Mouse TTPEIHSIFLEGHTFFVRNHR QASLEISPITFLTAQTLLID
Pig TSPEVHSIFLEGHTFLVRHHR QASLEISPLTFLTAQTFLMD
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
20 – 2351
Coagulation factor VIII
Chain
20 – 1332
Factor VIIIa heavy chain, 200 kDa isoform
Chain
20 – 759
Factor VIIIa heavy chain, 92 kDa isoform
Domain
20 – 348
F5/8 type A 1
Domain
206 – 348
Plastocyanin-like 2
Disulfide bond
267 – 348
Alternative sequence
9 – 2143
Missing. In isoform 2.
Beta strand
300 – 307
Literature citations
Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.
Higuchi M.; Kazazian H.H. Jr.; Kasch L.; Warren T.C.; McGinniss M.J.; Phillips J.A. III; Kasper C.; Janco R.; Antonarakis S.E.;
Proc. Natl. Acad. Sci. U.S.A. 88:7405-7409(1991)
Cited for: VARIANTS HEMA THR-108; VAL-110; GLY-285; HIS-301; SER-312; ARG-444; HIS-492; GLY-561; CYS-612; THR-723; PHE-1699; HIS-1800; TYR-1803; ASP-1941; SER-1941; HIS-2169; GLN-2228 AND CYS-2323;
Screen of 55 Slovenian haemophilia A patients: identification of 2 novel mutations (S-1R and IVS23+1G-->A) and discussion of mutation spectrum.
Strmecki L.; Benedik-Dolnicar M.; Vouk K.; Komel R.;
Hum. Mutat. 13:413-413(1999)
Cited for: VARIANTS HEMA ARG-19; HIS-301; LEU-308; HIS-2169; GLN-2228 AND GLN-2326;
Mutational-screening in the factor VIII gene resulting in the identification of three novel mutations, one of which is a donor splice mutation.
Moeller-Morlang K.; Tavassoli K.; Eigel A.; Pollmann H.; Horst J.;
Hum. Mutat. 13:504-504(1999)
Cited for: VARIANTS HEMA ARG-202 AND HIS-301;
Molecular pathology of haemophilia A in Turkish patients: identification of 36 independent mutations.
Timur A.A.; Guergey A.; Aktuglu G.; Kavakli K.; Canatan D.; Olek K.; Caglayan S.H.;
Haemophilia 7:475-481(2001)
Cited for: VARIANTS HEMA ASN-67; PHE-117; ALA-137; TYR-267; CYS-301; HIS-301; TYR-348; LYS-475; ALA-579; CYS-612; CYS-683; LEU-698; TRP-710; CYS-1708; HIS-1788; LEU-1876; TRP-2016; GLU-2045; CYS-2178; CYS-2182; HIS-2182; PRO-2182; ALA-2307 AND LEU-2323;
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.