UniProtKB/Swiss-Prot P00451: Variant p.Arg1708Cys

Coagulation factor VIII
Gene: F8
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Variant information Variant position:

1708 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 Arginine (R) to Cysteine (C) at position 1708 (R1708C, p.Arg1708Cys). 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 (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 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; East Hartford; severe/moderate/mild; abolishes thrombin cleavage at the light chain. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs111033613 [ dbSNP | Ensembl ]

Sequence information Variant position:

1708 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:

SVEMKKEDFDIYDEDENQSP R SFQKKTRHYFIAAVERLWDY 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                         SVEMKKEDFDIYDEDENQSPRSFQKKTRHYFIAAVERLWDY

                              SIEMKREDFDIYGDYENQGLRSFQKKTRHYFIAAVERLWDY

Mouse                         TIETI-EDFDIYSEDIKQGPRSFQQKTRHYFIAAVERLWDY

Pig                           STETKGEDFDIYGEDENQDPRSFQKRTRHYFIAAVEQLWDY

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	1668 – 2351	Factor VIIIa light chain
Site	1708 – 1709	Cleavage; by thrombin
Modified residue	1699 – 1699	Sulfotyrosine
Alternative sequence	9 – 2143	Missing. In isoform 2.

Literature citations
Purification and characterization of factor VIII 1,689-Cys: a nonfunctional cofactor occurring in a patient with severe hemophilia A.
O'Brien D.P.; Tuddenham E.G.;
Blood 73:2117-2122(1989)
Cited for: VARIANT HEMA CYS-1708; Characterization of a thrombin cleavage site mutation (Arg 1689 to Cys) in the factor VIII gene of two unrelated patients with cross-reacting material-positive hemophilia A.
Arai M.; Higuchi M.; Antonarakis S.E.; Kazazian H.H. Jr.; Phillips J.A. III; Janco R.L.; Hoyer L.W.;
Blood 75:384-389(1990)
Cited for: VARIANT HEMA CYS-1708; Characterization of mutations in the factor VIII gene by direct sequencing of amplified genomic DNA.
Higuchi M.; Wong C.; Kochhan L.; Olek K.; Aronis S.; Kasper C.K.; Kazazian H.H. Jr.; Antonarakis S.E.;
Genomics 6:65-71(1990)
Cited for: VARIANTS HEMA PHE-1699 AND CYS-1708; Detection and characterisation of two missense mutations at a cleavage site in the factor VIII light chain.
Schwaab R.; Ludwig M.; Kochhan L.; Oldenburg J.; McVey J.H.; Egli H.; Brackmann H.H.; Olek K.;
Thromb. Res. 61:225-234(1991)
Cited for: VARIANTS HEMA CYS-1708 AND HIS-1708; Screening for mutations in haemophilia A patients by multiplex PCR-SSCP, Southern blotting and RNA analysis: the detection of a genetic abnormality in the factor VIII gene in 30 out of 35 patients.
Pieneman W.C.; Deutz-Terlouw P.P.; Reitsma P.H.; Brieet E.;
Br. J. Haematol. 90:442-449(1995)
Cited for: VARIANTS HEMA HIS-217; ILE-299; ASN-450; TRP-546; CYS-612; VAL-705; CYS-1708; TRP-2016 AND ARG-2119; Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: family studies indicate a mutation type-dependent sex ratio of mutation frequencies.
Becker J.; Schwaab R.; Moeller-Taube A.; Schwaab U.; Schmidt W.; Brackmann H.H.; Grimm T.; Olek K.; Oldenburg J.;
Am. J. Hum. Genet. 58:657-670(1996)
Cited for: VARIANTS HEMA ARG-26; LYS-48; ASP-89; ASP-99; VAL-101; ARG-117; GLY-135; ASP-219; ARG-278; LEU-301; GLN-302 DEL; PRO-327; PRO-659; LEU-1012; GLU-1260; CYS-1708; ASN-1865; ARG-1873; THR-1971; TRP-2016; GLN-2228; LEU-2326 AND SER-2344; Factor VIII gene analysis in Japanese CRM-positive and CRM-reduced haemophilia A patients by single-strand conformation polymorphism.
Morichika S.; Shima M.; Kamisue S.; Tanaka I.; Imanaka Y.; Suzuki H.; Shibata H.; Pemberton S.; Gale K.; McVey J.; Tuddenham E.G.D.; Yoshioka A.;
Br. J. Haematol. 98:901-906(1997)
Cited for: VARIANTS HEMA CYS-274; CYS-492; ARG-498; HIS-550; ARG-686; CYS-1708; GLN-1960; HIS-2169; CYS-2178; ALA-2264 AND VAL-2304; Start of UK confidential haemophilia A database: analysis of 142 patients by solid phase fluorescent chemical cleavage of mismatch.
Waseem N.H.; Bagnall R.; Green P.M.; Giannelli F.;
Thromb. Haemost. 81:900-905(1999)
Cited for: VARIANTS HEMA CYS-24; ARG-26; TYR-113; SER-121; TRP-172; PRO-176; MET-181; VAL-214; THR-219; LYS-291; ALA-314; VAL-315; LYS-340; PHE-405; GLY-412; THR-470; GLU-474; ASN-478; CYS-484; GLY-490; ARG-498; TRP-546; CYS-550; HIS-561; ARG-584; THR-585; GLY-588; ASP-601; LYS-601; GLY-602; HIS-605; CYS-612; TRP-717; CYS-1708; GLN-1751; HIS-1800; CYS-1802; THR-1853; GLU-1864; PRO-1882; ILE-1888; LEU-1973; TRP-2016; ALA-2035; TYR-2040; CYS-2120; CYS-2145; HIS-2169; CYS-2178; HIS-2182; VAL-2183; VAL-2198; CYS-2248 AND GLY-2326; Lithuanian haemophilia A and B registry comprising phenotypic and genotypic data.
Ivaskevicius V.; Jurgutis R.; Rost S.; Muller A.; Schmitt C.; Wulff K.; Herrmann F.H.; Muller C.R.; Schwaab R.; Oldenburg J.;
Br. J. Haematol. 112:1062-1070(2001)
Cited for: VARIANTS HEMA VAL-255; GLU-323; CYS-391; CYS-550; VAL-586; CYS-1708; CYS-1800; ALA-1942; PRO-1963; CYS-2036; CYS-2124; ARG-2172; CYS-2182; GLN-2228 AND ALA-2307; 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; Mutation analysis in 51 patients with haemophilia A: report of 10 novel mutations and correlations between genotype and clinical phenotype.
Hill M.; Deam S.; Gordon B.; Dolan G.;
Haemophilia 11:133-141(2005)
Cited for: VARIANTS HEMA CYS-365; THR-470; SER-541; GLY-602; TRP-717; LYS-1701; CYS-1708; VAL-1727; ILE-1888; VAL-1966; TRP-2016; GLY-2018; LEU-2067; LEU-2162 AND HIS-2182;

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.